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Sample records for enantioselective synthesis application

  1. Enantioselective cyclization of enamide-ynes and application to the synthesis of the kopsifoline core

    PubMed Central

    Corkey, Britton K.; Heller, Stephen T.; Wang, Yi-Ming

    2013-01-01

    We report the palladium-catalyzed enantioselective cyclization of 1,6-enamidynes to form spirocyclic ring systems. We applied this methodology to the concise synthesis of the skeletal core of the kopsifoline alkaloids. PMID:23772095

  2. Enantioselective Synthesis of (+)-Peganumine A.

    PubMed

    Piemontesi, Cyril; Wang, Qian; Zhu, Jieping

    2016-09-01

    A gram-scale enantioselective total synthesis of (+)-peganumine A was accomplished in 7 steps from commercially available 6-methoxytryptamine. Key steps included (a) a Liebeskind-Srogl cross-coupling; (b) a one-pot construction of the tetracyclic skeleton from an ω-isocyano-γ-oxo-aldehyde via a sequence of an unprecedented C-C bond forming lactamization and a transannular condensation; (c) a one-pot organocatalytic process merging two achiral building blocks into an octacyclic structure via a sequence of enantioselective Pictet-Spengler reaction followed by a transannular cyclization. This last reaction created two spirocycles and a 2,7-diazabicyclo[2.2.1]heptan-3-one unit with excellent control of both the absolute and relative stereochemistry of the two newly created quaternary stereocenters. PMID:27558528

  3. Enantioselective Total Synthesis of (+)-Reserpine

    PubMed Central

    Rajapaksa, Naomi S.; McGowan, Meredeth A.; Rienzo, Matthew

    2013-01-01

    A catalytic, enantioselective synthesis of (+)-reserpine is reported. The route features a highly diastereoselective, chiral catalyst-controlled formal aza-Diels–Alder reaction between a 6-methoxytryptamine-derived dihydro-β-carboline and an enantioenriched α-substituted enone to form a key tetracyclic intermediate. This approach addresses the challenge of setting the C3 stereogenic center by using catalyst control. Elaboration of the tetracycle to (+)-reserpine includes an intramolecular aldol cyclization and a highly diastereoselective hydrogenation of a sterically hindered enoate. PMID:23331099

  4. Enantioselective Total Synthesis of (+)-Psiguadial B.

    PubMed

    Chapman, Lauren M; Beck, Jordan C; Wu, Linglin; Reisman, Sarah E

    2016-08-10

    The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C(sp(3))-H alkenylation reaction to strategically forge the C1-C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]decane terpene framework. PMID:27452034

  5. Enantioselective synthesis of endohedral metallofullerenes.

    PubMed

    Sawai, Koji; Takano, Yuta; Izquierdo, Marta; Filippone, Salvatore; Martín, Nazario; Slanina, Zdenek; Mizorogi, Naomi; Waelchli, Markus; Tsuchiya, Takahiro; Akasaka, Takeshi; Nagase, Shigeru

    2011-11-01

    Endohedral metallofullerenes are promising materials in biomedical and material sciences. In particular, they are of interest as agents for magnetic resonance imaging (MRI), photovoltaic devices, and semimetallic components. The synthesis of chiral endofullerenes represents one step further in the potential use of these carbon allotropes; however, this step has not been addressed so far. In this regard, enantiopure endofullerenes are expected to open new avenues in fields in which chirality is a key issue. Here, the synthesis and characterization of the first chiral endohedral metallofullerenes, namely, chiral bis-adducts of La@C(72), are reported. Eight optically active isomers were obtained by enantioselective 1,3-dipolar cycloaddition of a N-metalated azomethine ylide onto a non-isolated-pentagon rule metallofullerene derivative, La@C(72)(C(6)H(3)Cl(2)), catalyzed by a copper chiral complex. The chiral bis-adducts of La@C(72), isolated by nonchiral HPLC, showed optical purities as high as 98% as revealed by the remarkable positive or negative Cotton effects observed in the circular dichroic spectra.

  6. Enantioselective biotransformations of nitriles in organic synthesis.

    PubMed

    Wang, Mei-Xiang

    2015-03-17

    The hydration and hydrolysis of nitriles are valuable synthetic methods used to prepare carboxamides and carboxylic acids. However, chemical hydration and hydrolysis of nitriles involve harsh reaction conditions, have low selectivity, and generate large amounts of waste. Therefore, researchers have confined the scope of these reactions to simple nitrile substrates. However, biological transformations of nitriles are highly efficient, chemoselective, and environmentally benign, which has led synthetic organic chemists and biotechologists to study these reactions in detail over the last two decades. In nature, biological systems degrade nitriles via two distinct pathways: nitrilases catalyze the direct hydrolysis of nitriles to afford carboxylic acids with release of ammonia, and nitrile hydratases catalyze the conversion of nitriles into carboxamides, which then furnish carboxylic acids via hydrolysis in the presence of amidases. Researchers have subsequently developed biocatalytic methods into useful industrial processes for the manufacture of commodity chemicals, including acrylamide. Since the late 1990s, research by my group and others has led to enormous progress in the understanding and application of enantioselective biotransformations of nitriles in organic synthesis. In this Account, I summarize the important advances in enantioselective biotransformations of nitriles and amides, with a primary focus on research from my laboratory. I describe microbial whole-cell-catalyzed kinetic resolution of various functionalized nitriles, amino- and hydroxynitriles, and nitriles that contain small rings and the desymmetrization of prochiral and meso dinitriles and diamides. I also demonstrate how we can apply the biocatalytic protocol to synthesize natural products and bioactive compounds. These nitrile biotransformations offer an attractive and unique protocol for the enantioselective synthesis of polyfunctionalized organic compounds that are not readily obtainable by

  7. The Catalytic Enantioselective Total Synthesis of (+)-Liphagal**

    PubMed Central

    Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.; Kolding, Helene; Alleva, Jennifer L.; Stoltz, Brian M.

    2012-01-01

    Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwave-assisted metal catalysis, and an intramolecular aryne capture cyclization reaction. Pivotal to the successful completion of the synthesis was a sequence involving ring expansion from a [6-5-4] tricycle to a [6-7] bicyclic core followed by stereoselective hydrogenation of a sterically occluded tri-substituted olefin to establish the trans homodecalin system found in the natural product. PMID:21671325

  8. Enantioselective Total Synthesis of (-)-Alstoscholarisine A.

    PubMed

    Liang, Xiao; Jiang, Shi-Zhi; Wei, Kun; Yang, Yu-Rong

    2016-03-01

    We report a concise and highly enantioselective total synthesis of (-)-alstoscholarisine A (1), a recently isolated monoterpenoid indole alkaloid that has significant bioactivity in promoting adult neuronal stem cells proliferation. A highly enantioselective (99% ee), intramolecular Ir-catalyzed Friedel-Crafts alkylation of indole 9 with a secondary allylic alcohol was utilized to establish the first stereogenic center upon which the other three contiguous chiral centers were readily set by a highly stereoselective tandem 1,4-addition and aldol reaction. The key tetrahydropyran was constructed through a hemiacetal reduction, and the final aminal bridge was forged by a one-pot reductive amination/cyclization. The conciseness of this approach was highlighted by building core bonds in each step with a minimalist protecting group strategy. PMID:26882407

  9. Scalable, enantioselective taxane total synthesis

    PubMed Central

    Mendoza, Abraham; Ishihara, Yoshihiro; Baran, Phil S.

    2011-01-01

    Taxanes are a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel) — a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which possesses a suitable functional handle to access more oxidised members of its family. This route enabled a gram-scale preparation of the ”parent” taxane, taxadiene, representing the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The taxane family’s characteristic 6-8-6 tricyclic system containing a bridgehead alkene is forged via a vicinal difunctionalisation/Diels–Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed via substrate control. This study lays a critical foundation for a planned access to minimally oxidised taxane analogs and a scalable laboratory preparation of Taxol itself. PMID:22169867

  10. Enantioselective Synthesis of Pactamycin, a Complex Antitumor Antibiotic

    PubMed Central

    Malinowski, Justin T.; Sharpe, Robert J.; Johnson, Jeffrey S.

    2014-01-01

    Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally-intricate aminocyclopentitol antibiotic, displays potent anti-prolific properties across multiple phylogenetic domains, but is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Herein, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction/symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals fifteen steps and is immediately amenable for structural analog synthesis. PMID:23580525

  11. NHC-Cu-catalyzed addition of propargylboron reagents to phosphinoylimines. Enantioselective synthesis of trimethylsilyl-substituted homoallenylamides and application to the synthesis of S-(-)-cyclooroidin.

    PubMed

    Mszar, Nicholas W; Haeffner, Fredrik; Hoveyda, Amir H

    2014-03-01

    A catalytic method for the efficient and enantioselective addition of a 1-trimethylsilyl-substituted allene moiety to phosphinoylimines is presented. Transformations are promoted by 5.0 mol % of a copper complex of an N-heterocyclic carbene in the presence of a propargylboron reagent that can be readily prepared in multigram quantities. Within 10 min of reaction, products are obtained in up to 91% yield, 98% allene (vs propargyl) selectivity, and 98:2 enantiomeric ratio. An assortment of aldimines serve as suitable substrates. The phosphinoyl and silyl groups can be removed efficiently and orthogonally. The silylallene moiety may be transformed to versatile derivatives that are difficult to access via nonsilylated allenes. The special features and utility of the approach are highlighted through a succinct enantioselective synthesis of marine alkaloid S-(-)-cyclooroidin. PMID:24555471

  12. Design and Stereoselective Preparation of a New Class of Chiral Olefin Metathesis Catalysts and Application to Enantioselective Synthesis of Quebrachamine: Catalyst Development Inspired by Natural Product Synthesis

    PubMed Central

    Sattely, Elizabeth S.; Meek, Simon J.; Malcolmson, Steven J.; Schrock, Richard R.; Hoveyda, Amir H.

    2010-01-01

    A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of the natural product; the catalytic transformation proceeds with reasonable efficiency through the use of existing achiral Ru or Mo catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be inefficient and entirely nonselective in cases where the desired product is observed. In the present study, the synthesis route thus serves as a platform for the discovery of new olefin metathesis catalysts that allow for efficient completion of an enantioselective synthesis of quebrachamine. Accordingly, on the basis of mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands have been designed. The new catalysts provide significantly higher levels of activity than observed with the previously reported Ru- or Mo-based complexes. Enantiomerically enriched chiral alkylidenes are generated through diastereoselective reactions involving achiral Mo-based bispyrrolides and enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate the key enantioselective ring-closing metathesis step in the total synthesis of quebrachamine efficiently (1 mol % loading, 22 °C, 1 h, >98% conversion, 84% yield) and with high selectivity (98:2 er, 96% ee). PMID:19113867

  13. Enantioselective synthesis of metacycloprodigiosin via the “Wasserman pyrrole”

    PubMed Central

    Vega, Marvin M.; Crain, Diana M.; Konkol, Leah C.; Thomson, Regan J.

    2015-01-01

    A concise, nine-step enantioselective total synthesis of metacycloprodigiosin is reported. The synthesis provides increased step-efficiency over the previous racemic and enantioselective syntheses of this compound. Key features of the work include investigations into a convergent oxidative coupling reaction and subsequent ring-closing metathesis to deliver an advanced pyrrole intermediate we name the “Wasserman pyrrole” that can be converted to metacycloprodigiosin in one step. PMID:26120213

  14. Development of an Enantioselective Route towards the Lycopodium Alkaloids: Total Synthesis of Lycopodine

    PubMed Central

    Yang, Hua; Carter, Rich G.

    2010-01-01

    Synthesis of a C15-desmethyl tricycle core of lycopodine has been accomplished. Key steps in the synthetic sequence include organocatalytic, intramolecular Michael addition of a keto sulfone and a tandem 1,3-sulfonyl shift / Mannich cyclization to construct the tricyclic core ring system. Synthetic work towards this natural product family led to the development of N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide – an organocatalyst which facilitiates enantioselective, intramolecular Michael additions. A detailed mechanistic discussion is provided for both the intramolecular Michael addition and the sulfone rearrangement. Finally, the application of these discoveries to the enantioselective total synthesis of alkaloid lycopodine is described. PMID:20586477

  15. An enantioselective formal synthesis of montelukast sodium.

    PubMed

    Bollikonda, Satyanarayana; Mohanarangam, Saravanan; Jinna, Rajender Reddy; Kandirelli, Venkata Kiran Kumar; Makthala, Laxman; Sen, Saikat; Chaplin, David A; Lloyd, Richard C; Mahoney, Thomas; Dahanukar, Vilas Hareshwar; Oruganti, Srinivas; Fox, Martin E

    2015-04-17

    A formal synthesis of the antiasthma drug montelukast sodium is described, wherein the key chiral diol intermediate was accessed with greater convergence of the C-C bond-forming steps as compared to previous routes. Improved synthetic efficiency was achieved by deploying homogeneous metal-based catalysis in two pivotal steps. In the first, a tandem Mizoroki-Heck reaction and double-bond isomerization between a previously known allyl alcohol intermediate and a hindered 2-(2-halophenyl)propan-2-ol secured direct access to the 3-(2-(2-hydroxypropan-2-yl)phenyl)-1-phenylpropan-1-one moiety in the product. In the second step, asymmetric hydrogenation of the ketone functionality in the Mizoroki-Heck reaction product provided a convenient method to introduce the benzylic alcohol chiral center and obtain the desired chiral diol precursor of montelukast sodium. A detailed catalyst screening led to the identification of ((R)-Xyl-BINAP)((R,R)-DPEN)RuCl2 as a catalyst that afforded an enantioselectivity of 99% ee in the hydrogenation step on a multigram lab scale at a molar substrate:catalyst loading of 5000:1. PMID:25807000

  16. A Divergent Enantioselective Strategy for the Synthesis of Griseusins

    PubMed Central

    Zhang, Yinan; Ye, Qing; Wang, Xiachang; She, Qing-Bai; Thorson, Jon S.

    2015-01-01

    The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed C–H olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies. PMID:26230189

  17. Enantioselective synthesis of cis-decalins using organocatalysis and sulfonyl Nazarov reagents.

    PubMed

    Peña, Javier; Silveira-Dorta, Gastón; Moro, Rosalina F; Garrido, Narciso M; Marcos, Isidro S; Sanz, Francisca; Díez, David

    2015-04-10

    The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen's catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives.

  18. Enantioselective organocatalytic formal [3 + 3]-cycloaddition of alpha,beta-unsaturated aldehydes and application to the asymmetric synthesis of (-)-isopulegol hydrate and (-)-cubebaol.

    PubMed

    Hong, Bor-Cherng; Wu, Ming-Fun; Tseng, Hsing-Chang; Liao, Ju-Hsiou

    2006-05-25

    [reaction: see text] The first highly enantioselective organocatalyzed carbo [3 + 3] cascade cycloaddition of alpha,beta-unsaturated aldehydes is reported. Using this methodology, crotonaldehyde is converted to 6-hydroxy-4-methylcyclohex-1-enecarbaldehyde, which is used in the synthesis of (-)-isopulegol hydrate, (-)-cubebaol, and p-tolualdehyde as well as (-)-6-hydroxy-4-methyl-1-cyclohexene-1-methanol acetate, an intermediate in the total synthesis of lycopodium alkaloid magellanine. Other alpha,beta-unsaturated aldehydes give rise to chiral cyclohexadienes via formal [4 + 2] reactions. PMID:16706490

  19. Structure Elucidation of Nigricanoside A Through Enantioselective Total Synthesis

    PubMed Central

    Chen, Jie; Koswatta, Panduka; DeBergh, J. Robb; Fu, Peng; Pan, Ende; MacMillan, John B.; Ready, Joseph M.

    2016-01-01

    Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity. PMID:26877863

  20. Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

    PubMed

    Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

    2012-09-19

    α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

  1. Catalytic enantioselective 1,3-dipolar cycloadditions of azomethine ylides for biology-oriented synthesis.

    PubMed

    Narayan, Rishikesh; Potowski, Marco; Jia, Zhi-Jun; Antonchick, Andrey P; Waldmann, Herbert

    2014-04-15

    Cycloaddition reactions are among the most powerful methods for the synthesis of complex compounds. In particular, the development and application of the 1,3-dipolar cycloaddition, an important member of this reaction class, has grown immensely due to its powerful ability to efficiently build various five-membered heterocycles. Azomethine ylides are commonly used as dipoles for the synthesis of the pyrrolidine scaffold, which is an important motif in natural products, pharmaceuticals, and biological probes. The reaction between azomethine ylides and cyclic dipolarophiles allows access to polycyclic products with considerable complexity. The extensive application of the 1,3-dipolar cycloaddition is based on the fact that the desired products can be obtained with high yield in a regio- and stereocontrolled manner. The most attractive feature of the 1,3-dipolar cycloaddition of azomethine ylides is the possibility to generate pyrrolidines with multiple stereocenters in a single step. The development of enantioselective cycloadditions became a subject of intensive and impressive studies in recent years. Among many modes of stereoinduction, the application of chiral metal-ligand complexes has emerged as the most viable option for control of enantioselectivity. In chemical biology research based on the principle of biology-oriented synthesis (BIOS), compound collections are prepared inspired by natural product scaffolds. In BIOS, biological relevance is employed as the key criterion to generate hypotheses for the design and synthesis of focused compound libraries. In particular, the underlying scaffolds of natural product classes provide inspiration for BIOS because they define the areas of chemical space explored by nature, and therefore, they can be regarded as "privileged". The scaffolds of natural products are frequently complex and rich in stereocenters, which necessitates the development of efficient enantioselective methodologies. This Account highlights examples

  2. A broadly applicable NHC-Cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis.

    PubMed

    Gao, Fang; Carr, James L; Hoveyda, Amir H

    2014-02-01

    A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2':SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E. PMID:24467274

  3. Design, synthesis, and applications of potential substitutes of t-Bu-phosphinooxazoline in Pd-catalyzed asymmetric transformations and their use for the improvement of the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates.

    PubMed

    Bélanger, Étienne; Pouliot, Marie-France; Courtemanche, Marc-André; Paquin, Jean-François

    2012-01-01

    The design, synthesis, and applications of potential substitutes of t-Bu-PHOX in asymmetric catalysis is reported. The design relies on the incorporation of geminal substituents at C5 in combination with a substituent at C4 other than t-butyl (i-Pr, i-Bu, or s-Bu). Most of these new members of the PHOX ligand family behave similarly in terms of stereoinduction to t-Bu-PHOX in three palladium-catalyzed asymmetric transformations. Electronically modified ligands were also prepared and used to improve the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates.

  4. Enantioselective synthesis of primary 1-(aryl)alkylamines by nucleophilic 1,2-addition of organolithium reagents to hydroxyoxime ethers and application to asymmetric synthesis of G-protein-coupled receptor ligands.

    PubMed

    Atobe, Masakazu; Yamazaki, Naoki; Kibayashi, Chihiro

    2004-08-20

    (E)-Arylaldehyde oxime ethers bearing a (1S)-2-hydroxy-1-phenylethyl or (2R)-1-hydroxy-2-phenylethyl group as a chiral auxiliary, both derived from a single precursor, methyl (R)-mandelate, underwent nucleophilic addition with organolithium reagents via six-membered chelates to give the diastereomerically enriched (R)- and (S)-adducts, respectively, which, after chiral auxiliary removal by reductive N-O bond cleavage, led to the corresponding (R)- and (S)-1-(aryl)ethylamines. This organolithium addition protocol using methyllithium was applied in an enantiodivergent fashion to the preparation of both enantiomers of 1-(2-hydroxyphenyl)ethylamine, which has been previously used as an efficient chiral auxiliary for the synthesis of natural products in this laboratory. The synthetic utility of this methodology involving diastereoselective methyl addition was demonstrated by further application to the asymmetric synthesis of a new type of calcium receptor agonist (calcimimetics), (R)-(+)-NPS R-568 and its thio analogue. Furthermore, diastereoselective vinylation was accomplished by application of the hydroxy oxime ether-based protocol using vinyllithium, which allowed the development of the enantioselective synthesis of the NK-1 receptor antagonists, (+)-CP-99,994 and (+)-CP-122,721.

  5. Catalytic Enantioselective Synthesis of Quaternary Carbon Stereocenters

    PubMed Central

    Quasdorf, Kyle W.; Overman, Larry E.

    2015-01-01

    Preface Quaternary carbon stereocenters–carbon atoms to which four distinct carbon substituents are attached–are common features of molecules found in nature. However, prior to recent advances in chemical catalysis, there were few methods available for constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for synthesizing organic molecules containing such carbon atoms. This progress now makes it possible to selectively incorporate quaternary stereocenters in many high-value organic molecules for use in medicine, agriculture, and other areas. PMID:25503231

  6. Synthesis of tunable diamine ligands with spiro indane-2,2′-pyrrolidine backbone and their applications in enantioselective Henry reaction.

    PubMed

    Ćwiek, Rafał; Niedziejko, Piotr; Kałuża, Zbigniew

    2014-02-01

    Novel diamine ligands with spiro indane-2,2′-pyrrolidine scaffold were synthesized starting from Seebach’s oxazolidinone 6 and were subsequently employed in asymmetric Henry reaction. Following the initial experimental findings, further synthesis resulted in two types of spiro diamines, with varying substituents at both nitrogen atoms. Ligands of type A, containing a small substituent at N-1′ atom, and a large group at N-1 atom gave predominantly the S-configured β-nitroalcohol, while ligands of type B, with the reversed location of small and large substituents furnished the R-configured product. Both types of ligands turned out to be versatile catalysts for the Henry reaction between nitromethane and an assortment of aryl as well as alkyl aldehydes offering either S- (lig. A) or R-configured (lig. B) nitroalcohols in a good to high chemical yield and an excellent enantioselectivity up to 99% ee.

  7. Scalable enantioselective total synthesis of taxanes.

    PubMed

    Mendoza, Abraham; Ishihara, Yoshihiro; Baran, Phil S

    2011-11-06

    Taxanes form a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel), a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which has a suitable functional handle with which to access more oxidized members of its family. This route enables a gram-scale preparation of the 'parent' taxane--taxadiene--which is the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The characteristic 6-8-6 tricyclic system of the taxane family, containing a bridgehead alkene, is forged via a vicinal difunctionalization/Diels-Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed through substrate control. This study lays a critical foundation for a planned access to minimally oxidized taxane analogues and a scalable laboratory preparation of Taxol itself.

  8. Scalable enantioselective total synthesis of taxanes

    NASA Astrophysics Data System (ADS)

    Mendoza, Abraham; Ishihara, Yoshihiro; Baran, Phil S.

    2012-01-01

    Taxanes form a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel), a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which has a suitable functional handle with which to access more oxidized members of its family. This route enables a gram-scale preparation of the ‘parent’ taxane—taxadiene—which is the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The characteristic 6-8-6 tricyclic system of the taxane family, containing a bridgehead alkene, is forged via a vicinal difunctionalization/Diels-Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed through substrate control. This study lays a critical foundation for a planned access to minimally oxidized taxane analogues and a scalable laboratory preparation of Taxol itself.

  9. Enantioselective synthesis of cis-decalins using organocatalysis and sulfonyl Nazarov reagents.

    PubMed

    Peña, Javier; Silveira-Dorta, Gastón; Moro, Rosalina F; Garrido, Narciso M; Marcos, Isidro S; Sanz, Francisca; Díez, David

    2015-01-01

    The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen's catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives. PMID:25867826

  10. Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

    PubMed Central

    Evans, David A.; Burch, Jason D.; Hu, Essa; Jaeschke, Georg

    2012-01-01

    The enantioselective total synthesis of callipeltoside A is described. Two syntheses of the macrolactone subunit are included: the first relies upon an Ireland–Claisen rearrangement to generate the trisubstituted olefin geometry and the second utilizes an enantioselective vinylogous aldol reaction for this purpose. Enantioselective syntheses of the sugar and chlorocyclopropane side chain fragments are also disclosed. The relative and absolute stereochemistry of this natural product was determined by fragment coupling with the two enantiomers of the side chain fragment. PMID:22859865

  11. Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

    PubMed

    Huang, Linwei; Zhu, Jinbin; Jiao, Guangjun; Wang, Zheng; Yu, Xingxin; Deng, Wei-Ping; Tang, Wenjun

    2016-03-24

    Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram. PMID:26933831

  12. Catalytic enantioselective synthesis of vicinal dialkyl arrays.

    PubMed

    van Zijl, Anthoni W; Szymanski, Wiktor; López, Ferrnando; Minnaard, Adriaan J; Feringa, Ben L

    2008-09-19

    With a consecutive "asymmetric allylic alkylation (AAA)/cross-metathesis (CM)/conjugate addition (CA)" protocol it is possible to synthesize either stereoisomer of compounds containing a vicinal dialkyl array with excellent stereoselectivity. The versatility of this protocol in natural product synthesis is demonstrated in the preparation of the ant pheromones faranal and lasiol. PMID:18683977

  13. An efficient and general enantioselective synthesis of sphingosine, phythosphingosine, and 4-substituted derivatives.

    PubMed

    Llaveria, Josep; Díaz, Yolanda; Matheu, M Isabel; Castillón, Sergio

    2009-01-01

    A general and efficient protocol for the enantioselective synthesis of sphingosine, phythosphingosine, and 4-substituted derivatives was established. These compounds were obtained from a common intermediate prepared from butadiene monoepoxide by a synthetic sequence involving enantioselective allylic substitution, cross-metathesis, and dihydroxylation.

  14. Asymmetric synthesis of trifluoromethylated amines via catalytic enantioselective isomerization of imines.

    PubMed

    Wu, Yongwei; Deng, Li

    2012-09-01

    A new approach toward the asymmetric synthesis of optically active trifluoromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselectivities. PMID:22906148

  15. Enantioselective Total Synthesis of (+)-Lyngbyabellin M

    PubMed Central

    Pirovani, Rodrigo V.; Brito, Gilmar A.; Barcelos, Rosimeire C.; Pilli, Ronaldo A.

    2015-01-01

    Lyngbyabellin M is a non-ribosomal peptide synthetase/polyketide synthase derived metabolite isolated from the cyanobacterium M. bouillonii displaying thiazole rings and a distinct chlorinated octanoic acid chain. Its absolute configuration was proposed based on the comparison of its spectroscopic data with those of other representatives of this family of marine natural products, as well as degradation and derivatization studies. Here the first total synthesis of (+)-lyngbyabellin M is described based on the coupling of three key intermediates: two chiral thiazole moieties and an anti hydroxycarboxylic acid prepared stereoselectively via a boron enolate mediated aldol reaction directed by Masamune’s chiral auxiliary. PMID:26023838

  16. Enantioselective allylation of imines catalyzed by newly developed (-)-β-pinene-based π-allylpalladium catalyst: an efficient synthesis of (R)-α-propylpiperonylamine and (R)-pipecolic acid.

    PubMed

    Fernandes, Rodney A; Nallasivam, Jothi L

    2012-10-14

    A newly developed π-allylpalladium with a (-)-β-pinene framework and an isobutyl side chain catalyzed the enantioselective allylation of imines in good yields and enantioselectivities (20 examples, up to 98% ee). An efficient enantioselective synthesis of the (R)-α-propyl piperonylamine part of DMP 777, a human leukocyte elastase inhibitor and (R)-pipecolic acid have been achieved as a useful application of this methodology.

  17. Enantioselective Total Synthesis of (−)-Acylfulvene and (−)-Irofulven

    PubMed Central

    Siegel, Dustin S.; Piizzi, Grazia; Piersanti, Giovanni; Movassaghi, Mohammad

    2009-01-01

    We report our full account of the enantioselective total synthesis of (−)-acylfulvene (1) and (−)-irofulven (2), which features metathesis reactions for the rapid assembly of the molecular framework of these antitumor agents. We discuss (1) the application of an Evans’ Cu-catalyzed aldol addition reaction using a strained cyclopropyl ketenethioacetal, (2) an efficient enyne ring-closing metathesis (EYRCM) cascade reaction in a challenging setting, (3) the reagent IPNBSH for a late stage reductive allylic transposition reaction, and (4) the final RCM/dehydrogenation sequence for the formation of (−)-acylfulvene (1) and (−)-irofulven (2). PMID:19938810

  18. Organocatalytic, Enantioselective Synthesis of 1- and 3-Substituted Isochromans via Intramolecular Oxa-Michael Reaction of Alkoxyboronate: Synthesis of (+)-Sonepiprazole.

    PubMed

    Ravindra, Barnala; Maity, Sanjay; Das, Braja Gopal; Ghorai, Prasanta

    2015-07-17

    The enantioselective oxa-Michael reaction of alkoxyboronate strategy was demonstrated to provide a new and practical route to enantioriched 1- and 3-substituted isochromans using a chiral bifunctional organocatalyst. Furthermore, this methodology was extended to the enantioselective synthesis of (+)-sonepiprazole, a dopamine receptor antagonist.

  19. A Unified Approach for the Enantioselective Synthesis of the Brominated Chamigrene Sesquiterpenes.

    PubMed

    Burckle, Alexander J; Vasilev, Vasil H; Burns, Noah Z

    2016-09-12

    The brominated chamigrene sesquiterpenes constitute a large subclass of bromocyclohexane-containing natural products, yet no general enantioselective strategy for the synthesis of these small molecules exists. Herein we report a general strategy for accessing this family of secondary metabolites, including the enantioselective synthesis of (-)-α- and (-)-ent-β-bromochamigrene, (-)-dactylone, and (+)-aplydactone. Access to these molecules is enabled by a stereospecific bromopolyene cyclization initiated by the solvolysis of an enantiomerically enriched vicinal bromochloride. PMID:27506430

  20. Mo-catalyzed asymmetric olefin metathesis in target-oriented synthesis: Enantioselective synthesis of (+)-africanol

    PubMed Central

    Weatherhead, Gabriel S.; Cortez, G. A.; Schrock, Richard R.; Hoveyda, Amir H.

    2004-01-01

    Catalytic asymmetric ring-opening metathesis (AROM) provides an efficient method for the synthesis of a variety of optically enriched small organic molecules that cannot be easily prepared by alternative methods. The development of Mo-catalyzed AROM transformations that occur in tandem with ring-closing metathesis are described. The utility of the Mo-catalyzed AROM/ring-closing metathesis is demonstrated through an enantioselective approach to the synthesis of (+)-africanol. PMID:15056762

  1. Synthesis and application of a dual chiral [2.2]paracyclophane-based N-heterocyclic carbene in enantioselective β-boration of acyclic enones.

    PubMed

    Wang, Lei; Chen, Zhen; Ma, Manyuan; Duan, Wenzeng; Song, Chun; Ma, Yudao

    2015-11-21

    An enantioselective conjugate addition of boron to α,β-unsaturated ketones catalysed by either a N-heterocyclic carbene or a copper-carbene complex generated in situ from a new chiral bicyclic triazolium based on [2.2]paracyclophane is presented. The dual chiral carbene-copper catalyst has significant advantages over its carbene counterpart as an organocatalyst in asymmetric β-boration of acyclic enones, giving a variety of chiral β-boryl ketones in good yields and enantioselectivities. This is a successful example of employing the same N-heterocyclic carbene in one catalytic reaction as both an organocatalyst and a ligand for transition metal catalysis. PMID:26347490

  2. Versatile Enantioselective Synthesis of Functionalized Lactones via Copper-Catalyzed Radical Oxyfunctionalization of Alkenes.

    PubMed

    Zhu, Rong; Buchwald, Stephen L

    2015-07-01

    A versatile method for the rapid synthesis of diverse enantiomerically enriched lactones has been developed based on Cu-catalyzed enantioselective radical oxyfunctionalization of alkenes. The scope of this strategy encompasses a series of enantioselective difunctionalization reactions: oxyazidation, oxysulfonylation, oxyarylation, diacyloxylation, and oxyalkylation. These reactions provide straightforward access to a wide range of useful chiral lactone building blocks containing tetrasubstituted stereogenic centers, which are hard to access traditionally.

  3. A broadly applicable and practical oligomeric (salen) Co catalyst for enantioselective epoxide ring-opening reactions

    PubMed Central

    White, David E.; Tadross, Pamela M.; Lu, Zhe

    2014-01-01

    The (salen) Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen) Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen) Co monomer 1 for each reaction class. PMID:25045188

  4. Enantioselective total synthesis of (+)-Lingzhiol via tandem semipinacol rearrangement/Friedel-Crafts type cyclization.

    PubMed

    Chen, Dong; Xu, Wen-Dan; Liu, Hao-Miao; Li, Ming-Ming; Yan, Yong-Min; Li, Xiao-Nian; Li, Yan; Cheng, Yong-Xian; Qin, Hong-Bo

    2016-06-30

    Enantioselective total synthesis of (+)-Lingzhiol has been achieved. It is the first example of in tandem semipinacol rearrangement reactions, the migrated aryl group further reacting with the carbonyl oxonium electrophile to furnish a polycyclic skeleton. Our synthesis involves 13 steps and proceeds in 6% overall yield. PMID:27321202

  5. Copper-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes: synthesis of cyclopropylboronates.

    PubMed

    Parra, Alejandro; Amenós, Laura; Guisán-Ceinos, Manuel; López, Aurora; García Ruano, José Luis; Tortosa, Mariola

    2014-11-12

    A novel Cu-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes to afford nonracemic cyclopropylboronates is described. Trapping the cyclopropylcopper intermediate with electrophilic amines allows for the synthesis of cyclopropylaminoboronic esters and demonstrates the potential of the approach for the synthesis of functionalized cyclopropanes. PMID:25340304

  6. Enantioselective Total Synthesis of (−)-Nardoaristolone B via a Gold(I)-Catalyzed Oxidative Cyclization

    PubMed Central

    2015-01-01

    The first enantioselective total synthesis of (−)-nardoaristolone B is accomplished by the implementation of an enantio- and diastereoselective copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)-catalyzed oxidative cyclization (intermolecular oxidant), employed for the first time in total synthesis. PMID:25563976

  7. Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols

    NASA Astrophysics Data System (ADS)

    Shi, Shi-Liang; Wong, Zackary L.; Buchwald, Stephen L.

    2016-04-01

    The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

  8. Copper-catalyzed enantioselective stereodivergent synthesis of amino alcohols

    PubMed Central

    Shi, Shi-Liang; Wong, Zackary L.; Buchwald, Stephen L.

    2016-01-01

    The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. For this reason, it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation1,2. Despite many recent advances in asymmetric synthesis, the development of general and practical strategies to obtain all possible stereoisomers of an organic compound bearing multiple contiguous stereocenters remains a significant challenge3. In this manuscript, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, these amino alcohol products were synthesized using the sequential copper hydride-catalyzed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino alcohol products, which contain up to three contiguous stereocenters. Catalyst control and stereospecificity were simultaneously leveraged to attain exceptional control of the product stereochemistry. Beyond the utility of this protocol, the strategy demonstrated here should inspire the development of methods providing complete sets of stereoisomers for other valuable synthetic targets. PMID:27018656

  9. Development of a merged conjugate addition/oxidative coupling sequence. Application to the enantioselective total synthesis of metacycloprodigiosin and prodigiosin R1.

    PubMed

    Clift, Michael D; Thomson, Regan J

    2009-10-14

    A merged conjugate addition/oxidative coupling sequence that represents an efficient strategy for preparing structurally diverse pyrroles has been developed. Success of the method hinged upon the controlled oxidative coupling of unsymmetrical silyl bis-enol ether intermediates, formed by the 1,4-addition of a Grignard reagent with subsequent enolate trapping by a (chloro)silylenol ether. The process was applied to the first enantioselective syntheses of the biologically active pyrrolophane natural products, metacycloprodigiosin and prodigiosin R1.

  10. Catalytic enantioselective aziridoarylation of aryl cinnamyl ethers toward synthesis of trans-3-amino-4-arylchromans.

    PubMed

    Hajra, Saumen; Sinha, Debarshi

    2011-09-16

    Catalytic enantioselective one-pot aziridoarylation reaction of aryl cinnamyl ethers has been demonstrated in detail. Combination of suitable copper catalyst and chiral bis-oxazoline ligand was found to be very efficient for asymmetric aziridination followed by intramolecular arylation (Friedel-Crafts) reaction to provide a general and direct method for the synthesis of trans-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99:1), and enantioselectivity (up to 95% ee) with moderate yield. trans-3-Amino-4-arylchroman is an advanced intermediate for the synthesis of chromenoisoquinoline compounds such as doxanthrine, a potent and selective full agonist for the dopamine-D(1) receptor. PMID:21797274

  11. Characteristics of a new enantioselective thermostable dipeptidase from Brevibacillus borstelensis BCS-1 and its application to synthesis of a D-amino-acid-containing dipeptide.

    PubMed

    Baek, Dae Heoun; Song, Jae Jun; Kwon, Seok-Joon; Park, Chung; Jung, Chang-Min; Sung, Moon-Hee

    2004-03-01

    A new thermostable dipeptidase gene was cloned from the thermophile Brevibacillus borstelensis BCS-1 by genetic complementation of the D-Glu auxotroph Escherichia coli WM335 on a plate containing D-Ala-D-Glu. Nucleotide sequence analysis revealed that the gene included an open reading frame coding for a 307-amino-acid sequence with an M(r) of 35,000. The deduced amino acid sequence of the dipeptidase exhibited 52% similarity with the dipeptidase from Listeria monocytogenes. The enzyme was purified to homogeneity from recombinant E. coli WM335 harboring the dipeptidase gene from B. borstelensis BCS-1. Investigation of the enantioselectivity (E) to the P(1) and P(1)' site of Ala-Ala revealed that the ratio of the specificity constant (k(cat)/K(m)) for L-enantioselectivity to the P(1) site of Ala-Ala was 23.4 +/- 2.2 [E = (k(cat)/K(m))(L,D)/(k(cat)/K(m))(D,D)], while the D-enantioselectivity to the P(1)' site of Ala-Ala was 16.4 +/- 0.5 [E = (k(cat)/K(m))(L,D)/(k(cat)/K(m))(L,L)] at 55 degrees C. The enzyme was stable up to 55 degrees C, and the optimal pH and temperature were 8.5 and 65 degrees C, respectively. The enzyme was able to hydrolyze L-Asp-D-Ala, L-Asp-D-AlaOMe, Z-D-Ala-D-AlaOBzl, and Z-L-Asp-D-AlaOBzl, yet it could not hydrolyze D-Ala-L-Asp, D-Ala-L-Ala, D-AlaNH(2), and L-AlaNH(2.) The enzyme also exhibited beta-lactamase activity similar to that of a human renal dipeptidase. The dipeptidase successfully synthesized the precursor of the dipeptide sweetener Z-L-Asp-D-AlaOBzl.

  12. Catalytic asymmetric reductive coupling of alkynes and aldehydes: enantioselective synthesis of allylic alcohols and alpha-hydroxy ketones.

    PubMed

    Miller, Karen M; Huang, Wei-Sheng; Jamison, Timothy F

    2003-03-26

    A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes is described. Allylic alcohols are afforded with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process is complementary to existing methods of enantioselective alpha-hydroxy ketone synthesis. PMID:12643701

  13. A Green, Enantioselective Synthesis of Warfarin for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Wong, Terence C.; Sultana, Camille M.; Vosburg, David A.

    2010-01-01

    The enantioselective synthesis of drugs is of fundamental importance in the pharmaceutical industry. In this experiment, students synthesize either enantiomer of warfarin, a widely used anticoagulant, in a single step from inexpensive starting materials. Stereoselectivity is induced by a commercial organocatalyst, ("R","R")- or…

  14. Efficient Enantioselective Synthesis of Oxahelicenes Using Redox/Acid Cooperative Catalysts.

    PubMed

    Sako, Makoto; Takeuchi, Yoshiki; Tsujihara, Tetsuya; Kodera, Junpei; Kawano, Tomikazu; Takizawa, Shinobu; Sasai, Hiroaki

    2016-09-14

    An efficient and enantioselective synthesis of oxa[9]helicenes has been established via vanadium(V)-catalyzed oxidative coupling/intramolecular cyclization of polycyclic phenols. A newly developed vanadium complex cooperatively functions as both a redox and Lewis acid catalyst to promote the present sequential reaction and afford oxa[9]helicenes in good yields with up to 94% ee. PMID:27574874

  15. Quinidine thiourea-catalyzed enantioselective synthesis of β-nitrophosphonates: Beneficial effects of molecular sieves

    PubMed Central

    Abbaraju, Santhi; Bhanushali, Mayur; Zhao, Cong-Gui

    2011-01-01

    An efficient method for enantioselective synthesis of β-nitrophosphonates via the Michael addition of diphenyl phosphite to nitroalkenes using the readily available quinidine thiourea organocatalyst has been developed. The desired β-nitrophosphonates were obtained in good ee values. Molecular sieves were found to be crucial for achieving high reproducible yields in this reaction. PMID:21921970

  16. Asymmetric Synthesis of Trifluoromethylated Amines via Catalytic Enantioselective Isomerization of Imines

    PubMed Central

    Wu, Yongwei

    2012-01-01

    A new approach toward the asymmetric synthesis of optically active trifluromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselecitivities. PMID:22906148

  17. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

    PubMed Central

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  18. Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3beta inhibitor.

    PubMed

    Saitoh, Morihisa; Kunitomo, Jun; Kimura, Eiji; Yamano, Toru; Itoh, Fumio; Kori, Masakuni

    2010-09-01

    Glycogen synthase kinase 3beta (GSK-3beta) inhibitors are expected to be attractive therapeutic agents for the treatment of Alzheimer's disease (AD). Recently we discovered sulfoxides (S)-1 as a novel GSK-3beta inhibitor having in vivo efficacy. We investigated practical asymmetric preparation methods for the scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94% ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on gram scale.

  19. Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products.

    PubMed

    Ghislieri, Diego; Green, Anthony P; Pontini, Marta; Willies, Simon C; Rowles, Ian; Frank, Annika; Grogan, Gideon; Turner, Nicholas J

    2013-07-24

    The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine. PMID:23808566

  20. Enantioselective synthesis of the predominant AB ring system of the Schisandra nortriterpenoid natural products.

    PubMed

    Gockel, Birgit; Goh, Shermin S; Puttock, Emma J; Baars, Hannah; Chaubet, Guilhem; Anderson, Edward A

    2014-09-01

    An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a β-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.

  1. H8-BINOL chiral imidodiphosphoric acids catalyzed enantioselective synthesis of dihydroindolo-/-pyrrolo[1,2-a]quinoxalines.

    PubMed

    Fan, Yan-Sen; Jiang, Yi-Jun; An, Dong; Sha, Di; Antilla, Jon C; Zhang, Suoqin

    2014-12-01

    The first enantioselective synthesis of 5,6-dihydroindolo[1,2-a]quinoxalines is achieved by using a newly developed H8-BINOL-type imidodiphosphoric acid catalyst with low catalyst loading through efficient Pictet-Spengler-type reactions of indolyl anilines with ketones. This methodology also generates phenyl-4,5-dihydropyrrolo[1,2-a]quinoxalines with high yields and excellent enantioselectivities. Moreover, this method was utilized to synthesize an HIV-1 inhibitor with high yield and good enantioselectivity through a one-step procedure. PMID:25415871

  2. Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis

    PubMed Central

    Perdicchia, Dario; Christodoulou, Michael S.; Fumagalli, Gaia; Calogero, Francesco; Marucci, Cristina; Passarella, Daniele

    2015-01-01

    2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1. PMID:26712740

  3. Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids

    PubMed Central

    Canham, Stephen M.; Hafensteiner, Benjamin D.; Lebsack, Alec D.; May-Dracka, Tricia L.; Nam, Sangkil; Stearns, Brian A.; Overman, Larry E.

    2015-01-01

    A unified strategy for enantioselective total synthesis of all stereoisomers of the 2+2 family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetic intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (−)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine. PMID:26257440

  4. Enantioselective Synthesis of Dialkylated α-Hydroxy Carboxylic Acids through Asymmetric Phase-Transfer Catalysis.

    PubMed

    Duan, Shaobo; Li, Sanliang; Ye, Xinyi; Du, Nuan-Nuan; Tan, Choon-Hong; Jiang, Zhiyong

    2015-08-01

    In the presence of an L-tert-leucine-derived urea-ammonium salt as phase-transfer catalyst, a highly enantioselective alkylation of 5H-oxazol-4-ones with various benzyl bromides and allylic bromides has been developed to furnish catalytic asymmetric synthesis of biologically important dialkylated α-hydroxy carboxylic acids with a broad scope. This is the first example of an L-amino acid-derived urea-ammonium salt being used as a phase-transfer catalyst with excellent catalytic efficiency.

  5. Enantioselective Synthesis of Spirocyclohexadienones by NHC-Catalyzed Formal [3+3] Annulation Reaction of Enals.

    PubMed

    Yetra, Santhivardhana Reddy; Mondal, Santigopal; Mukherjee, Subrata; Gonnade, Rajesh G; Biju, Akkattu T

    2016-01-01

    The enantioselective synthesis of pyrazolone-fused spirocyclohexadienones was demonstrated by the reaction of α,β-unsaturated aldehydes with α-arylidene pyrazolinones under oxidative N-heterocyclic carbene (NHC)catalysis. This atom-economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all-carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC-catalyzed generation of chiral α,β-unsaturated acyl azoliums from enals, and base-mediated tandem generation of dienolate/enolate intermediates from pyrazolinones. PMID:26487242

  6. Enantioselective Synthesis and Profiling of Two Novel Diazabicyclooctanone β-Lactamase Inhibitors

    PubMed Central

    2014-01-01

    The enantioselective synthesis of two novel cyclopropane-fused diazabicyclooctanones is reported here. Starting from butadiene monoxide, the key enone intermediate 7 was prepared in six steps. Subsequent stereoselective introduction of the cyclopropane group and further transformation led to compounds 1a and 1b as their corresponding sodium salt. The great disparity regarding their hydrolytic stability was rationalized by the steric interaction between the cyclopropyl methylene and urea carbonyl. These two novel β-lactamase inhibitors were active against class A, C, and D enzymes. PMID:25313328

  7. Beyond Chemoselectivity: Catalytic Site-Selective Aldolization of Diketones and Exploitation for Enantioselective Alzheimer's Drug Candidate Synthesis.

    PubMed

    Nugent, Thomas C; Najafian, Foad Tehrani; Hussein, Hussein Ali El Damrany; Hussain, Ishtiaq

    2016-09-26

    Site selectivity, differentiating instances of the same functional group type on one substrate, represents a forward-looking theme within chemistry: reduced dependence on protection/deprotection protocols for increased overall yield and step-efficiency. Despite these potential benefits and the expanded tactical advantages afforded to synthetic design, site selectivity remains elusive and especially so for ketone-based substrates. Herein, site-selective intermolecular mono-aldolization has been demonstrated for an array of prochiral 4-keto-substituted cyclohexanones with concomitant regio-, diastereo-, and enantiocontrol. Importantly, the aldol products allow rapid access to molecularly complex ketolactones or keto-1,3-diols, respectively containing three and four stereogenic centers. The reaction conditions are of immediate practical value and general enough to be applicable to other reaction types. These findings are applied in the first enantioselective, formal, synthesis of a leading Alzheimer's research drug, a γ-secretase modulator (GSM), in the highest known yield. PMID:27546719

  8. Enantioselective Synthesis of Spirobarbiturate-Cyclohexenes through Phosphine-Catalyzed Asymmetric [4 + 2] Annulation of Barbiturate-Derived Alkenes with Allenoates.

    PubMed

    Liu, Honglei; Liu, Yang; Yuan, Chunhao; Wang, Guo-Peng; Zhu, Shou-Fei; Wu, Yang; Wang, Bo; Sun, Zhanhu; Xiao, Yumei; Zhou, Qi-Lin; Guo, Hongchao

    2016-03-18

    An enantioselective synthesis of pharmaceutically important spirobarbiturates has been achieved via spirocyclic chiral phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. With the use of this tool, various spirobarbiturate-cyclohexenes are obtained in good to excellent yields with excellent diastereo- and enantioselectivities. A wide range of α-substituted allenoates and barbiturate-derived alkenes were tolerated.

  9. Enantioselective Synthesis of 3a-Amino-Pyrroloindolines by Copper-Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines.

    PubMed

    Liu, Chuan; Yi, Ji-Cheng; Zheng, Zhong-Bo; Tang, Yong; Dai, Li-Xin; You, Shu-Li

    2016-01-11

    A direct asymmetric dearomative amination of tryptamines with O-(2,4-dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr-bisoxazoline complex as a catalyst, affording 3a-amino-pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (-)-psychotriasine in a highly concise manner. PMID:26603145

  10. Phormidolides B and C, cytotoxic agents from the sea: enantioselective synthesis of the macrocyclic core.

    PubMed

    Lorente, Adriana; Gil, Alejandro; Fernández, Rogelio; Cuevas, Carmen; Albericio, Fernando; Álvarez, Mercedes

    2015-01-01

    New cytotoxic polyketide macrolides named phormidolides B and C were isolated from a marine sponge of the Petrosiidae family collected off the coast of Pemba (Tanzania). The isolation, structure elucidation, and enantioselective synthesis of three diastereomers of the macrocyclic core is described herein. The described synthetic methodology started from 2-deoxy-D-ribose or 2-deoxy-L-ribose and afforded the desired macrocycles with high enantiomeric purity. The key step of the synthesis is the formation of the Z-trisubstituted double bond using a Julia-Kocienski olefination. The versatility of the synthetic methodology may provide access to other enantiopure macrocycles by making changes in the starting materials or chiral inductors.

  11. Enantioselective Synthesis of (−)-Maoecrystal V by Enantiodetermining C–H Functionalization

    PubMed Central

    2015-01-01

    The evolution of a program directed at the enantioselective total synthesis of maoecrystal V, a highly modified ent-kauranoid, is described. An early stage chiral auxiliary-directed asymmetric C–H functionalization for the construction of a key benzofuran intermediate enabled the first asymmetric synthesis of the natural enantiomer of maoecrystal V, confirming the assigned stereochemistry. A divergent course of the central intramolecular Diels–Alder reaction, which is dependent on the nature of the dienophile, initially led to the development of an unanticipated and previously unknown isomer of maoecrystal V, which we named maoecrystal ZG. In light of the reported selective and potent cytotoxic activity of maoecrystal V, the cytotoxic properties of maoecrystal ZG were also investigated. PMID:25409033

  12. Developing novel organocatalyzed aldol reactions for the enantioselective synthesis of biologically active molecules

    PubMed Central

    Bhanushali, Mayur; Zhao, Cong-Gui

    2011-01-01

    Aldol reaction is one of the most important methods for the formation of carbon-carbon bonds. Because of its significance and usefulness, asymmetric versions of this reaction have been realized with different approaches in the past. Over the last decade, the area of organocatalysis has made significant progresses. As one of most studied reactions in organocatalyses, organocatalyzed aldol reaction has emerged as a powerful tool for the synthesis of a large number of useful products in optically enriched forms. In this review, we summarize our efforts on the development of novel organocatalyzed aldol reactions for the enantioselective synthesis of biological active molecules. Literatures closely related to our studies are also covered. PMID:21918584

  13. Enantioselective Synthesis of N-PMP-1,2-dihydropyridines via Formal [4 + 2] Cycloaddition between Aqueous Glutaraldehyde and Imines.

    PubMed

    Ramaraju, Panduga; Mir, Nisar A; Singh, Deepika; Gupta, Vivek K; Kant, Rajni; Kumar, Indresh

    2015-11-20

    A simple and highly practical one-pot formal [4 + 2] cycloaddition approach for the enantioselective synthesis of N-PMP-1,2-dihydropyridines (DHPs) is described. This chemistry involves an amino-catalytic direct Mannich reaction/cyclization followed by IBX-mediated chemo- and regioselective oxidation sequence between readily available aqueous glutaraldehyde and imines under very mild conditions. A series of N-PMP-1,2-DHPs have been prepared in high yields and excellent enantioselectivity. This method also gives access to both enantiomers of 1,2-DHPs in surplus amount by shifting the catalyst configuration.

  14. Enantioselective small molecule synthesis by carbon dioxide fixation using a dual Brønsted acid/base organocatalyst.

    PubMed

    Vara, Brandon A; Struble, Thomas J; Wang, Weiwei; Dobish, Mark C; Johnston, Jeffrey N

    2015-06-17

    Carbon dioxide exhibits many of the qualities of an ideal reagent: it is nontoxic, plentiful, and inexpensive. Unlike other gaseous reagents, however, it has found limited use in enantioselective synthesis. Moreover, unprecedented is a tool that merges one of the simplest biological approaches to catalysis-Brønsted acid/base activation-with this abundant reagent. We describe a metal-free small molecule catalyst that achieves the three component reaction between a homoallylic alcohol, carbon dioxide, and an electrophilic source of iodine. Cyclic carbonates are formed enantioselectively.

  15. Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors.

    PubMed

    Shi, Shi-Liang; Wei, Xiao-Feng; Shimizu, Yohei; Kanai, Motomu

    2012-10-17

    A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Brønsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids. PMID:23039221

  16. Sulfur-directed enantioselective synthesis of functionalized dihydropyrans.

    PubMed

    Fernández de la Pradilla, Roberto; Tortosa, Mariola; Lwoff, Nadia; del Aguila, Miguel A; Viso, Alma

    2008-09-01

    The highly selective base-promoted cyclization of enantiopure sulfinyl dienols affords allylic sulfinyl dihydropyrans. The scope of this methodology, including the preparation of seven-membered rings, has been studied in depth. The reactivity of our sulfinyl dihydropyrans toward oxidation, imination, and dihydroxylation has been explored, and thus several routes to densely functionalized pyran derivatives have been outlined. The reactivity of allylic dihydropyranyl sulfones and sulfoximines in S(N)2' processes with organocuprates has been examined. The displacement products were obtained with good regio- and stereoselectivity and fair to good yields. The reactivity of these products to dihydroxylation opens new possibilities to access enantiopure polyhydroxylated tetrahydropyrans that could be of interest for the synthesis of natural products.

  17. A practical synthesis of renin inhibitor MK-1597 (ACT-178882) via catalytic enantioselective hydrogenation and epimerization of piperidine intermediate.

    PubMed

    Molinaro, Carmela; Shultz, Scott; Roy, Amélie; Lau, Stephen; Trinh, Thao; Angelaud, Rémy; O'Shea, Paul D; Abele, Stefan; Cameron, Mark; Corley, Ed; Funel, Jacques-Alexis; Steinhuebel, Dietrich; Weisel, Mark; Krska, Shane

    2011-02-18

    A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene-ester, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2.

  18. Enantioselective Cu-Catalyzed Arylation of Secondary Phosphine Oxides with Diaryliodonium Salts toward the Synthesis of P-Chiral Phosphines

    PubMed Central

    2016-01-01

    Catalytic synthesis of nonracemic P-chiral phosphine derivatives remains a significant challenge. Here we report Cu-catalyzed enantioselective arylation of secondary phosphine oxides with diaryliodonium salts for the synthesis of tertiary phosphine oxides with high enantiomeric excess. The new process is demonstrated on a wide range of substrates and leads to products that are well-established P-chiral catalysts and ligands. PMID:27689432

  19. Enantioselective Synthesis of (+)-Chamaecypanone C, a Novel Microtubule Inhibitor**

    PubMed Central

    Dong, Suwei; Hamel, Ernest; Bai, Ruoli; Covell, David G.; Beutler, John A.; Porco, John A.

    2009-01-01

    A number of bicyclo[2.2.2]octenone-containing natural products have been isolated from the heartwood of Chamaecyparis obtusa var. formosana (Figure 1) including the Diels-Alder adducts[1] obtunone (1),[2] chamaecypanone C (2),[3] and the [4+2] dimer (+)-3.[2],[4] Compound (+)-2 was shown to exhibit potent cytotoxicity against several human cancer cells including human oral epidermoid carcinoma (KB) (IC50 = 190 nM).[3] The biosynthesis of 2 was proposed[3] to occur via endo [4+2] cycloaddition between 1-hydroxymentha-3,5-dien-2-one 4 (Figure 2) and 1,3-bis-arylcyclopenta-1,3-diene 5, followed by oxidation to an enone in accord with literature reports of cyclopentadienes as biosynthetic precursors to natural products.[1b] An alternative possibility involving the corresponding cyclopentadienone 6 as dienophile may also be considered in light of known biosyntheses involving reactive cyclopentadienones.[5] Herein, we report a concise synthesis of both enantiomers of chamaecypanone C involving a retro-DA/DA cascade of dimer 3, obtained utilizing copper-mediated asymmetric oxidative dearomatization,[6] as well as biological studies documenting that the cytotoxic action of (+)-2 involves mitotic arrest as a consequence of its binding in the colchicine site of tubulin. PMID:19140149

  20. A practical and efficient route for the highly enantioselective synthesis of mexiletine analogues and novel beta-thiophenoxy and pyridyl ethers.

    PubMed

    Huang, Kun; Ortiz-Marciales, Margarita; Stepanenko, Viatcheslav; De Jesús, Melvin; Correa, Wildeliz

    2008-09-01

    A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues with use of 10% of spiroborate ester 6 as chirality transfer agent is presented. A variety of mexiletine analogues were prepared in good yield with excellent enantioselectivities (91-97% ee) from readily available starting materials. The developed methodology was also successfully applied for the synthesis of novel beta-amino ethers containing thiophenyl and pyridyl fragments. PMID:18690744

  1. Concise Enantioselective Total Synthesis of Cardiotonic Steroids 19-Hydroxysarmentogenin and Trewianin Aglycone.

    PubMed

    Kaplan, Will; Khatri, Hem Raj; Nagorny, Pavel

    2016-06-01

    The expedient and scalable approach to cardiotonic steroids carrying oxygenation at the C11- and C19-positions has been developed and applied to the total asymmetric synthesis of steroids 19-hydroxysarmentogenin and trewianin aglycone as well as to the assembly of the panogenin core. This new approach features enantioselective organocatalytic oxidation of an aldehyde, diastereoselective Cu(OTf)2-catalyzed Michael reaction/tandem aldol cyclizations, and one-pot reduction/transposition reactions allowing a rapid (7 linear steps) assembly of a functionalized cardenolide skeleton. The ability to quickly set this steroidal core with preinstalled functional handles and diversity elements eliminates the need for difficult downstream functionalizations and substantially improves the accessibility to the entire class of cardenolides and their derivatives for biological evaluation.

  2. Enantioselective carbenoid insertion into C(sp3)–H bonds

    PubMed Central

    Santiago, J V

    2016-01-01

    Summary The enantioselective carbenoid insertion into C(sp3)–H bonds is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. PMID:27340479

  3. Enantioselective Synthesis of Various Cyanohydrins Using Covalently Immobilized Preparations of Hydroxynitrile Lyase from Prunus dulcis.

    PubMed

    Alagöz, Dilek; Tükel, S Seyhan; Yildirim, Deniz

    2015-11-01

    The carrier-based and carrier-free (cross-linked enzyme aggregate) covalent immobilizations of Prunus dulcis hydroxynitrile lyase were investigated. The immobilized preparations were tested for enantioselective carbon-carbon bond formation activity in the biphasic medium. Of the tested preparations, only cross-linked enzyme aggregate of P. dulcis hydroxynitrile lyase (PdHNL-CLEA) achieved the synthesis of (R)-mandelonitrile with 93% yield and 99% enantiopurity. PdHNL-CLEA was also used in the synthesis of various (R)-cyanohydrins from corresponding aldehydes/ketones and hydrocyanic acid. When 4-methoxybenzaldehyde, 4-methyl benzaldehyde, and 4-hydroxybenzaldehyde were used as substrates, the yield-enantiomeric excess of corresponding (R)-cyanohydrins were obtained as 95-95, 85-79, and 2-25%, respectively, after 96 h at pH 4.0 and 5 °C. For acetophenone, 4-fluoroacetophenone, 4-chloroacetophenone, 4-bromoacetophenone, and 4-iodoacetophenone, the yield-enantiomeric excess of corresponding (R)-cyanohydrins were 1-99, 20-84, 11-95, 5-99, and 3-24%, respectively at the same conditions. The results demonstrate PdHNL-CLEA can be effectively used in the synthesis of (R)-mandelonitrile. PMID:26310798

  4. Enantioselective Synthesis of Various Cyanohydrins Using Covalently Immobilized Preparations of Hydroxynitrile Lyase from Prunus dulcis.

    PubMed

    Alagöz, Dilek; Tükel, S Seyhan; Yildirim, Deniz

    2015-11-01

    The carrier-based and carrier-free (cross-linked enzyme aggregate) covalent immobilizations of Prunus dulcis hydroxynitrile lyase were investigated. The immobilized preparations were tested for enantioselective carbon-carbon bond formation activity in the biphasic medium. Of the tested preparations, only cross-linked enzyme aggregate of P. dulcis hydroxynitrile lyase (PdHNL-CLEA) achieved the synthesis of (R)-mandelonitrile with 93% yield and 99% enantiopurity. PdHNL-CLEA was also used in the synthesis of various (R)-cyanohydrins from corresponding aldehydes/ketones and hydrocyanic acid. When 4-methoxybenzaldehyde, 4-methyl benzaldehyde, and 4-hydroxybenzaldehyde were used as substrates, the yield-enantiomeric excess of corresponding (R)-cyanohydrins were obtained as 95-95, 85-79, and 2-25%, respectively, after 96 h at pH 4.0 and 5 °C. For acetophenone, 4-fluoroacetophenone, 4-chloroacetophenone, 4-bromoacetophenone, and 4-iodoacetophenone, the yield-enantiomeric excess of corresponding (R)-cyanohydrins were 1-99, 20-84, 11-95, 5-99, and 3-24%, respectively at the same conditions. The results demonstrate PdHNL-CLEA can be effectively used in the synthesis of (R)-mandelonitrile.

  5. Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: Enantioselective synthesis of d-myo-inositol-6-phosphate

    PubMed Central

    Jordan, Peter A.; Kayser-Bricker, Katherine J.; Miller, Scott J.

    2010-01-01

    Despite the ubiquitous use of phosphoramidite chemistry in the synthesis of biophosphates, catalytic asymmetric phosphoramidite transfer remains largely unexplored for phosphate ester synthesis. We have discovered that a tetrazole-functionalized peptide, in the presence of 10-Å molecular sieves, functions as an enantioselective catalyst for phosphite transfer. This chemistry in turn has been used as the key step in a streamlined synthesis of myo-inositol-6-phosphate. Mechanistic insights implicate phosphate as a directing group for a highly selective kinetic resolution of a protected inositol monophosphate. This work represents a distinct and efficient method for the selective catalytic phosphorylation of natural products. PMID:20439750

  6. Enantioselective synthesis of biphenols from 1,4-diketones by traceless central-to-axial chirality exchange.

    PubMed

    Guo, Fenghai; Konkol, Leah C; Thomson, Regan J

    2011-01-12

    A method for the enantioselective synthesis of biphenols from readily prepared 1,4-diketones is reported. Key to the success of this method is the highly selective transfer of central to axial chirality during a double aromatization event triggered by BF(3)·OEt(2). On the basis of X-ray crystallographic data, a stereochemical model for this chirality exchange process is put forth. PMID:21141997

  7. Enantioselective Synthesis of Biphenols from 1,4-Diketones by Traceless Central-to-Axial Chirality Exchange

    PubMed Central

    Guo, Fenghai; Konkol, Leah C.; Thomson, Regan J.

    2010-01-01

    A method for the enantioselective synthesis of biphenols from readily prepared 1,4-diketones is reported. Key to the success of this method is the highly selective transfer of central to axial chirality during a double aromatization event triggered by BF3•OEt2. Based upon X-ray crystallographic data, a stereochemical model for this chirality exchange process is put forth. PMID:21141997

  8. Organocatalyzed enantioselective synthesis of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylates

    PubMed Central

    Ramireddy, Naresh; Abbaraju, Santhi; Zhao, Cong-Gui

    2011-01-01

    The organocatalyzed enantioselective synthesis of biologically active 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate derivatives was achieved using bifunctional cinchona alkaloids as the catalysts. Using quinine thiourea as the catalyst, the tandem Michael addition-cyclization reaction between 1,3-cyclohexanediones and alkylidenecyanoacetate derivatives gives the desired products in high yields (up to 92%) and good ee values (up to 82%). PMID:22081731

  9. Catalytic Enantioselective Olefin Metathesis in Natural Product Synthesis. Chiral Metal-Based Complexes that Deliver High Enantioselectivity and More

    PubMed Central

    Malcolmson, Steven J.; Meek, Simon J.; Zhugralin, Adil R.

    2012-01-01

    Chiral olefin metathesis catalysts enable chemists to access enantiomerically enriched small molecules with high efficiency; synthesis schemes involving such complexes can be substantially more concise than those that would involve enantiomerically pure substrates and achiral Mo alkylidenes or Ru-based carbenes. The scope of research towards design and development of chiral catalysts is not limited to discovery of complexes that are merely the chiral versions of the related achiral variants. A chiral olefin metathesis catalyst, in addition to furnishing products of high enantiomeric purity, can offer levels of efficiency, product selectivity and/or olefin stereoselectivity that are unavailable through the achiral variants. Such positive attributes of chiral catalysts (whether utilized in racemic or enantiomerically enriched form) should be considered as general, applicable to other classes of transformations. PMID:19967680

  10. Enantioselective synthesis of angularly substituted 1-azabicylic rings: coupled dynamic kinetic epimerization and chirality transfer.

    PubMed

    Aron, Zachary D; Ito, Tatsuya; May, Tricia L; Overman, Larry E; Wang, Jocelyn

    2013-10-01

    A new strategy for enantioselective synthesis of azacyclic molecules in which dynamic kinetic equilibration of diastereomeric iminium ions precedes a stereochemistry-determining sigmatropic rearrangement is reported. The method is illustrated by the synthesis, in high enantiomeric purity (generally 95-99% ee), of a variety of 1-azabicyclic molecules containing angular allyl or 3-substituted 2-propenyl side chains adjacent to nitrogen and up to three stereogenic centers. In these products, the size of the carbocyclic ring is varied widely (5-12 membered); however, useful yields are obtained in forming 1-azabicyclic products containing only fused pyrrolidine and piperidine rings. Chirality transfer from substituents at carbons 1 and 2 of the 3-butenylamine fragment of the starting material is investigated, with methyl and phenyl substituents at the allylic position shown to provide exquisite stereocontrol (generally 98-99% chirality transfer). An attractive feature of the method is the ability to carry out the key transformation in the absence of solvent. Illustrated also is the high yielding conversion of four such products to a new family of bicyclic β-amino acids of high enantiomeric purity.

  11. Enantioselective synthesis of tatanans A-C and reinvestigation of their glucokinase-activating properties

    NASA Astrophysics Data System (ADS)

    Xiao, Qing; Jackson, Jeffrey J.; Basak, Ashok; Bowler, Joseph M.; Miller, Brian G.; Zakarian, Armen

    2013-05-01

    The tatanans are members of a novel class of complex sesquilignan natural products recently isolated from the rhizomes of Acorus tatarinowii Schott plants. Tatanans A, B and C have previously been reported to have potent glucokinase-activating properties that exceed the in vitro activity of known synthetic antidiabetic agents. Here, using a series of sequential [3,3]-sigmatropic rearrangements, we report the total synthesis of tatanan A in 13 steps and 13% overall yield. We also complete a concise enantioselective total synthesis of more complex, atropisomeric tatanans B and C via a distinct convergent strategy based on a palladium-catalysed diastereotopic aromatic group differentiation (12 steps, 4% and 8% overall yield, respectively). A plausible biosynthetic relationship between acyclic tatanan A and spirocyclic tatanans B and C is proposed and probed experimentally. With sufficient quantities of the natural products in hand, we undertake a detailed functional characterization of the biological activities of tatanans A-C. Contrary to previous reports, our assays utilizing pure recombinant human enzyme demonstrate that tatanans do not function as allosteric activators of glucokinase.

  12. Enantioselective Synthesis of Spirobarbiturate-Cyclohexenes through Phosphine-Catalyzed Asymmetric [4 + 2] Annulation of Barbiturate-Derived Alkenes with Allenoates.

    PubMed

    Liu, Honglei; Liu, Yang; Yuan, Chunhao; Wang, Guo-Peng; Zhu, Shou-Fei; Wu, Yang; Wang, Bo; Sun, Zhanhu; Xiao, Yumei; Zhou, Qi-Lin; Guo, Hongchao

    2016-03-18

    An enantioselective synthesis of pharmaceutically important spirobarbiturates has been achieved via spirocyclic chiral phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. With the use of this tool, various spirobarbiturate-cyclohexenes are obtained in good to excellent yields with excellent diastereo- and enantioselectivities. A wide range of α-substituted allenoates and barbiturate-derived alkenes were tolerated. PMID:26937706

  13. Enantioselective Synthesis of α-Hydroxy Amides and β-Amino Alcohols from α-Keto Amides.

    PubMed

    Mamillapalli, N Chary; Sekar, Govindasamy

    2015-12-14

    Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral Cu(II)/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives. PMID:26503887

  14. Enantioselective TADMAP-Catalyzed Carboxyl Migration Reactions for the Synthesis of Stereogenic Quaternary Carbon

    PubMed Central

    Shaw, Scott A.; Aleman, Pedro; Christy, Justin; Kampf, Jeff W.; Va, Porino

    2008-01-01

    The chiral, nucleophilic catalyst TADMAP (1) has been prepared from 3-lithio-4-dimethylamino-pyridine (5) and triphenylacetaldehyde (3), followed by acylation and resolution. TADMAP catalyzes the carboxyl migration of oxazolyl, furanyl, and benzofuranyl enol carbonates with good to excellent levels of enantioselection. The oxazole reactions are especially efficient, and are used to prepare chiral lactams (23) and lactones (30) containing a quaternary asymmetric carbon. TADMAP-catalyzed carboxyl migrations in the indole series are relatively slow and proceed with inconsistent enantioselectivity. Modeling studies (B3LYP/6-31G*) have been used in qualitative correlations of catalyst conformation, reactivity, and enantioselectivity. PMID:16417383

  15. Pt-Catalyzed Enantioselective Cycloisomerization for the Synthesis of Planar-Chiral Ferrocene Derivatives.

    PubMed

    Shibata, Takanori; Uno, Ninna; Sasaki, Tomoya; Kanyiva, Kyalo Stephen

    2016-08-01

    Enantioselective cycloisomerization of 2-ethynyl-1-ferrocenylbenzene derivatives proceeded by using a chiral cationic platinum catalyst at room temperature. The intramolecular reaction gave planar-chiral naphthalene- and anthracene-fused ferrocene derivatives with high to excellent ee.

  16. Enantioselective synthesis of benzazepinoindoles bearing trifluoromethylated quaternary stereocenters catalyzed by chiral spirocyclic phosphoric acids.

    PubMed

    Li, Xuejian; Chen, Di; Gu, Haorui; Lin, Xufeng

    2014-07-18

    The first highly enantioselective iso-Pictet-Spengler reaction of C-2-linked o-aminobenzylindoles with trifluoromethyl ketones was developed using chiral spirocyclic phosphoric acids as organocatalysts, which afforded optically active benzazepinoindoles bearing trifluoromethylated quaternary stereocenters. PMID:24890313

  17. Synthesis of Metal-Organic Zeolites with Homochirality and High Porosity for Enantioselective Separation.

    PubMed

    Xu, Zhong-Xuan; Liu, Liyang; Zhang, Jian

    2016-07-01

    Using lactic acid derivatives as chiral ligands, a pair of unprecedented homochiral metal-organic zeolites have been synthesized that feature zeotype CAN topology and have high porosity for enantioselective separation of racemates.

  18. Enantioselective synthesis of 4H-pyranonaphthoquinones via sequential squaramide and silver catalysis.

    PubMed

    Kaya, Uğur; Chauhan, Pankaj; Hack, Daniel; Deckers, Kristina; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-01-28

    An enantioselective one-pot Michael addition/hydroalkoxylation reaction between 2-hydroxy-1,4-naphthoquinones and alkyne-tethered nitroalkenes catalyzed by a cinchona-derived squaramide and a silver(I) salt has been developed. The sequential protocol provides a direct access to 4H-pyranonaphthoquinones in moderate to very good yields and good to excellent enantioselectivities at a very low catalyst loading (0.5 mol%) of the squaramide.

  19. Enantioselective Intermolecular Cyclopropanations for the Synthesis of Chiral Pyrimidine Carbocyclic Nucleosides.

    PubMed

    Xie, Ming-Sheng; Zhou, Peng; Niu, Hong-Ying; Qu, Gui-Rong; Guo, Hai-Ming

    2016-09-01

    A direct route to chiral cyclopropylpyrimidine carbocyclic nucleoside analogues has been reported via highly enantioselective intermolecular cyclopropanation reactions of N1-vinylpyrimidines with α-diazoesters. With chiral ruthenium(II)-phenyloxazoline complex (2 mol %) as the catalyst, cyclopropyl pyrimidine nucleoside analogues could be obtained in good yields (71-96% yields) with high levels of diastereo- and enantioselectivities (10:1 to >20:1 dr and 96-99% ee) in 1 min. PMID:27526779

  20. Enantioselective synthesis of 4H-pyranonaphthoquinones via sequential squaramide and silver catalysis.

    PubMed

    Kaya, Uğur; Chauhan, Pankaj; Hack, Daniel; Deckers, Kristina; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-01-28

    An enantioselective one-pot Michael addition/hydroalkoxylation reaction between 2-hydroxy-1,4-naphthoquinones and alkyne-tethered nitroalkenes catalyzed by a cinchona-derived squaramide and a silver(I) salt has been developed. The sequential protocol provides a direct access to 4H-pyranonaphthoquinones in moderate to very good yields and good to excellent enantioselectivities at a very low catalyst loading (0.5 mol%) of the squaramide. PMID:26660230

  1. Core-structure-inspired asymmetric addition reactions: enantioselective synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents.

    PubMed

    Li, Shen; Ma, Jun-An

    2015-11-01

    Dihydrobenzoxazinones and dihydroquinazolinones are the core units present in many anti-HIV agents, such as Efavirenz, DPC 961, DPC 963, and DPC 083. All these molecules contain a trifluoromethyl moiety at the quaternary stereogenic carbon center with S configuration. The enantioselective addition of carbon nucleophiles to ketones or cyclic ketimines could serve as a key step to access these molecules. This tutorial review provides an overview of significant advances in the synthesis of dihydrobenzoxazinone- and dihydroquinazolinone-based anti-HIV agents and relative analogues, with an emphasis on asymmetric addition reactions for the establishment of the CF3-containing quaternary carbon centers.

  2. 3D chiral nanoplasmonics: fabrication, chiroptic engineering, mechanism, and application in enantioselection (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Huang, Zhifeng

    2015-09-01

    Chirality does naturally exist, and the building blocks of life (e.g. DNA, proteins, peptides and sugars) are usually chiral. Chirality inherently imposes chemical/biological selectivity on functional molecules; hence the discrimination in molecular chirality from an enantiomer to the other mirror image (i.e. enantioselection) has fundamental and application significance. Enantiomers interact with left and right handed circularly polarized light in a different manner with respect to optical extinction; hence, electronic circular dichroism (ECD) has been widely used for enantioselection. However, enantiomers usually have remarkably low ECD intensity, mainly owing to the small electric transition dipole moment induced by molecular sizes compared to the ECD-active wavelength in the UV-visible-near IR region. To enhance ECD magnitude, recently it has being developed 3D chiral nanoplasmonic structures having a helical path, and the dimensions are comparable to the ECD wavelength. However, it is still ambiguous the origin of 3D chiroplasmonics, and there is a lack of studying the interaction of 3D chiroplasmoncs with enantiomers for the application of enantioselection. Herein, we will present a one-step fabrication of 3D silver nanospirals (AgNSs) via low-substrate-temperature glancing angle deposition. AgNSs can be deposited on a wide range of substrates (including transparent and flexible substrates), in an area on the order of cm2. A set of spiral dimensions (such as spiral pitches, number of turns and handedness) have been easily engineered to tune the chiroptic properties, leading to studying the chiroplasmonic principles together with finite element simulation and the LC model. At the end, it will be demonstrated that 3D chiroplasmonics can differentiate molecular chirality of enantiomers with dramatic enhancement in the anisotropy g factor. This study opens a door to sensitively discriminate enantiomer chirality.

  3. Cationic Pd(II)-Catalyzed Cyclization of N-Tosyl-aniline Tethered Allenyl Aldehydes with Arylboronic Acids: Diastereo- and Enantioselective Synthesis of Tetrahydroquinoline Derivatives.

    PubMed

    Zhang, Xiaojuan; Han, Xiuling; Lu, Xiyan

    2015-08-01

    An efficient cyclization of N-tosyl-aniline tethered allenyl aldehydes and arylboronic acids catalyzed by cationic palladium complex is developed. This annulation reaction provides a convenient process for the synthesis of 3,4-cis-1,2,3,4-tetrahydroquinoline derivatives in high yields with excellent diastereoselectivity and enantioselectivity.

  4. Organocatalytic enantioselective Michael-Michael-Michael-aldol condensation reactions: control of five stereocenters in a quadruple-cascade asymmetric synthesis of highly functionalized hexahydrophenanthrenes.

    PubMed

    Raja, Arun; Hong, Bor-Cherng; Lee, Gene-Hsiang

    2014-11-01

    A cascade organocatalysis has been developed for the enantioselective synthesis of a highly functionalized hexahydrophenanthrene-2-carbaldehyde containing five contiguous stereogenic centers with high diastereoselectivity and high enantioselectivity (>99% ee). The one-pot method comprises a cascade of organocatalytic Michael-Michael-Michael-aldol reactions of 2-methyl-1,5-dinitro-3-((E)-2-nitrovinyl)benzene and α,β-unsaturated aldehydes (e.g., cinnamaldehyde). The structure and absolute configuration of a product were confirmed by X-ray analysis of an appropriate derivative.

  5. Catalytic Enantioselective Carbon-Oxygen Bond Formation: Phosphine-Catalyzed Synthesis of Benzylic Ethers via the Oxidation of Benzylic C-H Bonds.

    PubMed

    Ziegler, Daniel T; Fu, Gregory C

    2016-09-21

    Benzylic alcohols and ethers are common subunits in bioactive molecules, as well as useful intermediates in organic chemistry. In this Communication, we describe a new approach to the enantioselective synthesis of benzylic ethers through the chiral phosphine-catalyzed coupling of two readily available partners, γ-aryl-substituted alkynoates and alcohols, under mild conditions. In this process, the alkynoate partner undergoes an internal redox reaction. Specifically, the benzylic position is oxidized with good enantioselectivity, and the alkyne is reduced to the alkene. PMID:27618638

  6. Enantioselective Synthesis of 4- and 6-Azaindolines by a Cation-Directed Cyclization

    PubMed Central

    2016-01-01

    Functionalized 4- and 6-azaindolines are accessible with high levels of enantioselectivity by the cation-directed cyclization of aminopyridine-derived imines via phase-transfer catalysis. The extension of this methodology to diastereoselective cyclizations is also described. PMID:27709963

  7. Enantioselective Friedel-Crafts alkylation for synthesis of 2-substituted indole derivatives.

    PubMed

    Zhang, Yulong; Liu, Xiaohua; Zhao, Xiaohu; Zhang, Jianlin; Zhou, Lin; Lin, Lili; Feng, Xiaoming

    2013-12-14

    An efficient catalytic asymmetric intermolecular C2 Friedel-Crafts alkylation reaction between N-methyl skatole and β,γ-unsaturated α-ketoesters has been realized by a chiral N,N'-dioxide-Ni(II) complex. The corresponding indole derivatives were obtained in good yield (up to 96%) with excellent enantioselectivities (up to 99% ee) under mild reaction conditions. PMID:24158312

  8. Enantioselective synthesis of adamantylalanine and carboranylalanine and their incorporation into the proteasome inhibitor bortezomib.

    PubMed

    de Bruin, Gerjan; Mock, Elliot D; Hoogendoorn, Sascha; van den Nieuwendijk, Adrianus M C H; Mazurek, Jaroslaw; van der Marel, Gijsbert A; Florea, Bogdan I; Overkleeft, Herman S

    2016-03-14

    The incorporation of adamantylalanine and carboranylalanine at the P2 site of bortezomib is well tolerated and provided potent cell permeable proteasome inhibitors with increased off-rates compared to bortezomib. Adamantylalanine and carboranylalanine were synthesized enantioselectively by an asymmetric Strecker reaction on Ellmans tert-butyl sulfinimines.

  9. Enantioselective synthesis of 3-hydroxy oxindoles by ytterbium-catalysed decarboxylative addition of β-ketoacids to isatins.

    PubMed

    Duan, Zhiqiang; Han, Jianlin; Qian, Ping; Zhang, Zirui; Wang, Yi; Pan, Yi

    2013-10-14

    A ytterbium(III)-indapybox catalysed enantioselective decarboxylative addition reaction of β-ketoacids to isatins is described. The biologically important 3-hydroxy oxindoles were obtained in high yields and excellent enantioselectivities.

  10. Copper-Catalyzed Borylative Aromatization of p-Quinone Methides: Enantioselective Synthesis of Dibenzylic Boronates

    PubMed Central

    2015-01-01

    In this report, we establish that DM-Segphos copper(I) complexes are efficient catalysts for the enantioselective borylation of para-quinone methides. This method provides straightforward access to chiral monobenzylic and dibenzylic boronic esters, with enantiomeric ratios up to 96:4, using a commercially available chiral phosphine. Standard manipulations of the C–B bond afford a variety of chiral diaryl derivatives. PMID:27088045

  11. Enantioselective synthesis of hindered cyclic dialkyl ethers via catalytic oxa-Michael/Michael desymmetrization†

    PubMed Central

    Corbett, Michael T.; Johnson, Jeffrey S.

    2014-01-01

    An asymmetric oxa-Michael/Michael cascade reaction of p-quinols and α,β-unsaturated aldehydes provides access to hindered dialkyl ethers. A highly enantioselective oxa-Michael addition of a tertiary alcohol precedes an intramolecular cyclohexadienone desymmetrization, which allows for the concomitant formation of four contiguous stereocenters in a single step. The highly functionalized bicyclic frameworks are rapidly obtained from simple starting materials with good diastereoselection and serve as valuable precursors for further manipulation. PMID:24683449

  12. A Multicomponent Ni-, Zr-, and Cu-Catalyzed Strategy for Enantioselective Synthesis of Alkenyl-Substituted Quaternary Carbons**

    PubMed Central

    McGrath, Kevin P.

    2014-01-01

    The availability of enantiomerically enriched carbonyl-containing compounds is essential to the synthesis of biologically active molecules. Since catalytic enantioselective conjugate addition (ECA) reactions directly generate the latter valuable class of molecules, the design and development of such protocols represents a compelling objective in modern chemistry. Herein, we disclose the first solution to the problem of ECA of alkenyl groups to acyclic trisubstituted enones, an advance achieved by adopting an easily modifiable and fully catalytic approach. The requisite alkenylaluminum reagents are synthesized with exceptional site- and/or stereoselectivity by a Ni-catalyzed hydroalumination process, and the necessary enones are prepared through a site- and stereoselective zirconocene-catalyzed carboalumination/acylation reaction. The all-catalytic procedure is complete within four hours, furnishing the desired products in up to 77% overall yield and 99:1 enantiomeric ratio. PMID:24474609

  13. Divergent synthesis of chiral heterocycles via sequencing of enantioselective three-component reactions and one-pot subsequent cyclization reactions.

    PubMed

    Tang, Min; Xing, Dong; Huang, Haoxi; Hu, Wenhao

    2015-07-01

    A highly efficient sequencing of catalytic asymmetric three-component reactions of alcohols, diazo compounds and aldimines/aldehydes with one-pot subsequent cyclization reactions was reported. The development of a robust and versatile Rh(ii)/Zr(iv)-BINOL co-catalytic system not only gives high diastereo- and enantioselective controls of the three-component reaction, but also shows excellent functionality tolerances that allow a wide range of functionalities to be pre-installed in each component and readily undergo one-pot subsequent cyclization reactions, thus providing rapid and diversity-oriented synthesis (DOS) of different types of chiral nitrogen- and/or oxygen-containing polyfunctional heterocycles. PMID:25864421

  14. Enantioselective microbial synthesis of the indigenous natural product (-)-α-bisabolol by a sesquiterpene synthase from chamomile (Matricaria recutita).

    PubMed

    Son, Young-Jin; Kwon, Moonhyuk; Ro, Dae-Kyun; Kim, Soo-Un

    2014-10-15

    (-)-α-Bisabolol, a sesquiterpene alcohol, is a major ingredient in the essential oil of chamomile (Matricaria recutita) and is used in many health products. The current supply of (-)-α-bisabolol is mainly dependent on the Brazilian candeia tree (Eremanthus erythropappus) by distillation or by chemical synthesis. However, the distillation method using the candeia tree is not sustainable, and chemical synthesis suffers from impurities arising from undesirable α-bisabolol isomers. Therefore enzymatic synthesis of (-)-α-bisabolol is a viable alternative. In the present study, a cDNA encoding (-)-α-bisabolol synthase (MrBBS) was identified from chamomile and used for enantioselective (-)-α-bisabolol synthesis in yeast. Chamomile MrBBS was identified by Illumina and 454 sequencing, followed by activity screening in yeast. When MrBBS was expressed in yeast, 8 mg of α-bisabolol was synthesized de novo per litre of culture. The structure of purified α-bisabolol was elucidated as (S,S)-α-bisabolol [or (-)-α-bisabolol]. Although MrBBS possesses a putative chloroplast-targeting peptide, it was localized in the cytosol, and a deletion of its N-terminal 23 amino acids significantly reduced its stability and activity. Recombinant MrBBS showed kinetic properties comparable with those of other sesquiterpene synthases. These data provide compelling evidence that chamomile MrBBS synthesizes enantiopure (-)-α-bisabolol as a single sesquiterpene product, opening a biotechnological opportunity to produce (-)-α-bisabolol. PMID:25048207

  15. Ethylene in Organic Synthesis. Repetitive Hydrovinylation of Alkenes for Highly Enantioselective Syntheses of Pseudopterosins

    PubMed Central

    Mans, Daniel J.; Cox, G. Adam; RajanBabu, T. V.

    2011-01-01

    In this report we highlight the significant potential of ethylene as a reagent for the introduction of a vinyl group with excellent stereoselectivity at three different stages in the synthesis of a broad class of natural products, best exemplified by syntheses of pseudopterosins. The late-stage applications of the asymmetric hydrovinylation reaction further illustrate the compatibility of the catalyst with complex functional groups. We also show that depending on the choice of the catalyst, it is possible to either enhance or even completely reverse the inherent diastereoselectivity in the reactions of advanced chiral intermediates. This should enable the synthesis of diastereomeric analogs of several classes of medicinally relevant compounds that are not readily accessible by the existing methods, which depend on ‘substrate-control’ for the installation of many of the chiral centers, especially in molecules of this class. PMID:21449569

  16. Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

    PubMed Central

    Martín-Rodríguez, María; de Cózar, Abel

    2011-01-01

    Summary The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial. PMID:21915198

  17. Noncovalent Substrate-Directed Enantioselective Heck Reactions: Synthesis of S- and P-Stereogenic Heterocycles.

    PubMed

    de Azambuja, Francisco; Carmona, Rafaela C; Chorro, Tomaz H D; Heerdt, Gabriel; Correia, Carlos Roque D

    2016-08-01

    S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five-membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process. PMID:27273079

  18. Enantioselective Synthesis of Both Epimers at C-21 in the Proposed Structure of Cytotoxic Macrolide Callyspongiolide.

    PubMed

    Ghosh, Arun K; Kassekert, Luke A

    2016-07-01

    Both epimers at C-21 in the proposed structure of (+)-callyspongiolide have been synthesized in a convergent and enantioselective manner. The 14-membered macrolide with a sensitive C2-C3 cis-olefin functionality was installed by a Yamaguchi macrolactonization of hydroxyl alkynoic acid followed by hydrogenation over Lindlar's catalyst. The C5 methyl stereocenter was constructed by a ring-closing olefin metathesis followed by addition of methyl cuprate to an α,β-unsaturated δ-lactone. Other key reactions are chiral Corey-Bakshi-Shibata (CBS) reduction and Sonogashira coupling to conjoin the macrocyclic core and side chain. PMID:27331421

  19. Enantioselective Protonation

    PubMed Central

    Mohr, Justin T.; Hong, Allen Y.; Stoltz, Brian M.

    2010-01-01

    Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods to achieve enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proven useful for the preparation of a number of valuable organic compounds. PMID:20428461

  20. An approach to seco-prezizaane sesquiterpenoids: enantioselective total synthesis of (+)-1S-minwanenone.

    PubMed

    Mehta, Goverdhan; Shinde, Harish M

    2012-09-21

    A strategy of general applicability toward seco-prezizaane sesquiterpenes, from a chiral, tricyclic synthon, readily available via an enzymatic resolution step from the Diels-Alder adduct of cyclopentadiene and p-benzoquinone, has been devised. Our approach enables harnessing of the stereochemical proclivities of the norbornyl system to install the desired stereochemistry at the key stereogenic centers. Recourse to an interesting stratagem to realign a stereochemical divergence into stereoreconvergence forms the cornerstone of our successful approach. The first total synthesis of (+)-1S-minwanenone, a prototypical member of seco-prezizaane subclass, has been accomplished. PMID:22897237

  1. Improved cyclopropanation activity of histidine-ligated cytochrome P450 enables the enantioselective formal synthesis of levomilnacipran.

    PubMed

    Wang, Z Jane; Renata, Hans; Peck, Nicole E; Farwell, Christopher C; Coelho, Pedro S; Arnold, Frances H

    2014-06-23

    Engineering enzymes capable of modes of activation unprecedented in nature will increase the range of industrially important molecules that can be synthesized through biocatalysis. However, low activity for a new function is often a limitation in adopting enzymes for preparative-scale synthesis, reaction with demanding substrates, or when a natural substrate is also present. By mutating the proximal ligand and other key active-site residues of the cytochrome P450 enzyme from Bacillus megaterium (P450-BM3), a highly active His-ligated variant of P450-BM3 that can be employed for the enantioselective synthesis of the levomilnacipran core was engineered. This enzyme, BM3-Hstar, catalyzes the cyclopropanation of N,N-diethyl-2-phenylacrylamide with an estimated initial rate of over 1000 turnovers per minute and can be used under aerobic conditions. Cyclopropanation activity is highly dependent on the electronic properties of the P450 proximal ligand, which can be used to tune this non-natural enzyme activity. PMID:24802161

  2. Anionic cyclodextrins as versatile hosts for pharmaceutical nanotechnology: Synthesis, drug delivery, enantioselectivity, contrast agents for MRI.

    PubMed

    Mavridis, Irene M; Yannakopoulou, Konstantina

    2015-08-15

    The review presents a full library of single-isomer primary rim per-carboxylate- and per-sulfate-α-, -β- and -γ-cyclodextrin (CD) derivatives and their potential for pharmaceutical nanotechnology. Recent advances in cyclodextrin chemistry have enabled robust methods for the synthesis of single-isomer anionic CDs. Numerous nanobio-applications have been already reported for these negatively charged derivatives, which alone or in combination with other biodegradable molecular platforms can become important carriers for targeted drug delivery and release. Specialized applications are also discussed, such as chiral separations, as well as the ability of per-6-carboxylated-cyclodextrins to coordinate with metal cations and especially with lanthanide cations that makes them candidates as contrast agents for Magnetic Resonance Imaging.

  3. Enantioselective Construction of Tetrahydroquinolin-5-one-Based Spirooxindole Scaffold via an Organocatalytic Asymmetric Multicomponent [3 + 3] Cyclization.

    PubMed

    Zhu, Qiu-Ning; Zhang, Yu-Chen; Xu, Meng-Meng; Sun, Xiao-Xue; Yang, Xue; Shi, Feng

    2016-09-01

    The first catalytic enantioselective construction of biologically important tetrahydroquinolin-5-one-based spirooxindole has been developed via a chiral cinchona alkaloid catalyzed asymmetric three-component [3 + 3] cyclization of cyclic enaminone, isatin, and malononitrile, which afforded a series of tetrahydroquinolin-5-one-based spirooxindoles in high yields and with excellent enantioselectivities (up to 99% yield, 97:3 er). This reaction could be applicable to large-scale synthesis of enantioenriched tetrahydroquinolin-5-one-based spirooxindoles. This synthetic methodology will not only provide a unique approach for the construction of chiral tetrahydroquinolin-5-one-based spirooxindole scaffolds but also increase our understanding of catalytic enantioselective multicomponent reactions.

  4. Practical and Broadly Applicable Catalytic Enantioselective Additions of Allyl-B(pin) Compounds to Ketones and α-Ketoesters.

    PubMed

    Robbins, Daniel W; Lee, KyungA; Silverio, Daniel L; Volkov, Alexey; Torker, Sebastian; Hoveyda, Amir H

    2016-08-01

    A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.

  5. Catalytic enantioselective synthesis of chiral organic compounds of ultra-high purity of >99% ee

    PubMed Central

    NEGISHI, Ei-ichi; XU, Shiqing

    2015-01-01

    Shortly after the discovery of Zr-catalyzed carboalumination of alkynes in 1978, we sought expansion of the scope of this reaction so as to develop its alkene version for catalytic asymmetric C–C bond formation, namely the ZACA (Zr-catalyzed asymmetric carboalumination of alkenes). However, this seemingly easy task proved to be quite challenging. The ZACA reaction was finally discovered in 1995 by suppressing three competitive side reactions, i.e., (i) cyclic carbometalation, (ii) β-H transfer hydrometalation, and (iii) alkene polymerization. The ZACA reaction has been used to significantly modernize and improve syntheses of various natural products including deoxypolypropionates and isoprenoids. This review focuses on our recent progress on the development of ZACA–lipase-catalyzed acetylation–transition metal-catalyzed cross-coupling processes for highly efficient and enantioselective syntheses of a wide range of chiral organic compounds with ultra-high enantiomeric purities. PMID:26460317

  6. Enantioselective synthesis and olfactory evaluation of 13-alkyl-substituted alpha-ionones.

    PubMed

    Luparia, Marco; Boschetti, Paolo; Piccinini, Francesca; Porta, Alessio; Zanoni, Giuseppe; Vidari, Giovanni

    2008-06-01

    To study the influence of the steric bulk of the substituents at C(5) on the olfactory characteristics of alpha-ionone, the (S)-antipodes of compounds 8-10 were synthesized starting from (S)-alpha-cyclogeraniol (14a). The latter was available in useful preparative yield with 95% ee by enantioselective lipase-PS-mediated acetylation of the racemic mixture. Key step in the conversion of 14a to 8-10 was an S(N)2'-type reaction of an organocuprate on the allylic phosphate 20, which appears to be a general method for the introduction of an alkyl substituent at the cyclohexene C=C bond of ionones. Olfactory evaluation showed that, compared to the parent (S)-alpha-ionone (1), the odor strength and fragrance facets of the three analogues 8-10 are significantly influenced by the bulkiness of the substituent at C(13), giving further evidence that hydrophobic interactions of this group play a significant role in the chemoreception of ionones. In particular, the odor of the ethyl derivative 8 was found to be significantly stronger than that of the parent (S)-alpha-ionone (1).

  7. Simple Organic Molecules as Catalysts for Enantioselective Synthesis of Amines and Alcohols

    PubMed Central

    Silverio, Daniel L.; Torker, Sebastian; Pilyugina, Tatiana; Vieira, Erika M.; Snapper, Marc L.; Haeffner, Fredrik; Hoveyda, Amir H.

    2012-01-01

    The discovery of new catalysts that can generate complex organic compounds via enantioselective transformations is central to advances in the life sciences;i for this reason, many chemists try to discover catalysts that can be used to produce chiral molecules with a strong preference for one mirror image isomer.ii The ideal catalyst should be devoid of precious elementsiii and should bring reactions to completion in a few hours using operationally simple procedures. In this manuscript, we introduce a set of small organic molecules that can catalyze reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which can be used to synthesize more complex, biologically active molecules. A distinguishing feature of this new catalyst class is the presence of a 'key' proton embedded within their structure. The catalyst is derived from the abundant amino acid valine and was prepared in large quantities in four steps using inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mol % catalyst in less than six hours at room temperature to generate products in >85% yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents render this advance vital to future progress in chemistry, biology and medicine. PMID:23407537

  8. An enantioselective amidase from Burkholderia multivorans for the stereoselective synthesis of esfenvalerate.

    PubMed

    Lee, Sang-Hyun; Park, Oh-Jin; Shin, Hyun-Jae

    2014-07-01

    Using racemic (R,S)-2-(4-chlorophenyl)-3-methylbutyramide, an intermediate for the chiral pyrethroid insecticide Esfenvalerate, as a sole nitrogen source in a minimal medium, several strains with high enatioselectivity (≥98%) were isolated by enrichment techniques. One of the strains, LG 31-3, was identified as Burkholderia multivorans, based on physiological and morphological tests by a standardized Biolog station for carbon source utilization. A novel amidase was purified from B. mutivorans LG 31-3 and characterized. The enzyme exhibited (S)- selective amidase activity on racemic (R,S)-2-(4-chlorophenyl)-3-methylbutyramide. Addition of the racemic amide induced the production of the enantioselective amidase. The molecular mass of the amidase on SDS-PAGE analysis was shown to be 50 kDa. The purified amidase was subjected to proteolytic digestion with a modified trypsin. The N-terminal and internal amino acid sequences of the purified amidase showed a high sequence homology with those deduced from a gene named YP_366732.1 encoding indole acetimide hydrolase from Burkholderia sp. 383. PMID:24722372

  9. Catalytic enantioselective synthesis of naturally occurring butenolides via hetero-allylic alkylation and ring closing metathesis.

    PubMed

    Mao, Bin; Geurts, Koen; Fañanás-Mastral, Martín; van Zijl, Anthoni W; Fletcher, Stephen P; Minnaard, Adriaan J; Feringa, Ben L

    2011-03-01

    An efficient catalytic asymmetric synthesis of chiral γ-butenolides was developed based on the hetero-allylic asymmetric alkylation (h-AAA) in combination with ring closing metathesis (RCM). The synthetic potential of the h-AAA-RCM protocol was illustrated with the facile synthesis of (-)-whiskey lactone, (-)-cognac lactone, (-)-nephrosteranic acid, and (-)-roccellaric acid.

  10. Catalytic enantioselective synthesis of naturally occurring butenolides via hetero-allylic alkylation and ring closing metathesis.

    PubMed

    Mao, Bin; Geurts, Koen; Fañanás-Mastral, Martín; van Zijl, Anthoni W; Fletcher, Stephen P; Minnaard, Adriaan J; Feringa, Ben L

    2011-03-01

    An efficient catalytic asymmetric synthesis of chiral γ-butenolides was developed based on the hetero-allylic asymmetric alkylation (h-AAA) in combination with ring closing metathesis (RCM). The synthetic potential of the h-AAA-RCM protocol was illustrated with the facile synthesis of (-)-whiskey lactone, (-)-cognac lactone, (-)-nephrosteranic acid, and (-)-roccellaric acid. PMID:21268603

  11. N-Heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals with aldimines: highly enantioselective synthesis of dihydropyridinones.

    PubMed

    Gao, Zhong-Hua; Chen, Xiang-Yu; Zhang, Han-Ming; Ye, Song

    2015-08-01

    The N-heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals and aldimines was developed to give the corresponding dihydropyridinones in good yields with excellent enantioselectivities. PMID:26121224

  12. Williamson Ether Synthesis with Phenols at a Tertiary Stereogenic Carbon: Formal Enantioselective Phenoxylation of β-Keto Esters.

    PubMed

    Shibatomi, Kazutaka; Kotozaki, Manato; Sasaki, Nozomi; Fujisawa, Ikuhide; Iwasa, Seiji

    2015-09-28

    The enantioselective formation of α-aryloxy-β-keto esters is described for the first time. Lewis acid catalyzed enantioselective chlorination of β-keto esters and subsequent SN 2 reactions with phenols yielded α-aryloxy-β-keto esters with up to 96% ee. Favorskii rearrangement of α-chloro-β-keto esters was also found to give 1,2-diesters with slightly reduced enantiopurity.

  13. Molecular modeling application on hapten epitope prediction: an enantioselective immunoassay for ofloxacin optical isomers.

    PubMed

    Mu, Hongtao; Lei, Hongtao; Wang, Baoling; Xu, Zhenlin; Zhang, Chijian; Ling, Li; Tian, Yuanxin; Hu, Jinsheng; Sun, Yuanming

    2014-08-01

    To deepen our understanding of the physiochemical principles that govern hapten-antibody recognition, ofloxacin enantiomers were chosen as a model for epitope prediction of small molecules. In this study, two monoclonal antibodies (mAbs) mAb-WR1 and mAb-MS1 were raised against R-ofloxacin and S-ofloxacin, respectively. The enantioselective mAbs have a high sensitivity and specificity, and the enantioselectivity is not affected by heterologous coating format reactions. The epitopes of the ofloxacin isomers were predicted using the hologram quantitative structure-activity relationship (HQSAR) and comparative molecular field analysis (CoMFA) approaches. The results consistently show that the epitope of the chiral hapten should be primarily composed of the oxazine ring and the piperazinyl ring and mAbs recognize the hapten from the side of this moiety. The enantioselectivity of mAbs is most likely due to the steric hindrance caused by the stereogenic center of the epitope. Modeling of chiral hapten-protein mimics reveals that ofloxacin isomers remain upright on the surface of the carrier protein. Suggestions to improve the enantioselectivity of antibodies against ofloxacin isomers were also proposed. This study provided a simple, efficient, and general method for predicting the epitopes of small molecules via molecular modeling. The epitope predictions for small molecules may create a theoretical guide for hapten design.

  14. Enantioselective Synthesis of Polysubstituted Spiro-nitroprolinates Mediated by a (R,R)-Me-DuPhos·AgF-Catalyzed 1,3-Dipolar Cycloaddition.

    PubMed

    Cayuelas, Alberto; Ortiz, Ricardo; Nájera, Carmen; Sansano, José M; Larrañaga, Olatz; de Cózar, Abel; Cossío, Fernando P

    2016-06-17

    The synthesis of constrained spirocycles is achieved effectively by means of 1,3-dipolar cyclodditions employing α-imino γ-lactones as azomethine ylide precursors and nitroalkenes as dipolarophiles. The complex formed by (R,R)-Me-DuPhos 18 and AgF is the most efficient bifunctional catalyst. Final spiro-nitroprolinates cycloadducts are obtained in good to moderate yields and both high diastereo- and enantioselectivities. Density functional theory (DFT) calculations supported the expected absolute configuration as well as other stereochemical parameters. PMID:27268161

  15. Enantioselective Synthesis of Polysubstituted Spiro-nitroprolinates Mediated by a (R,R)-Me-DuPhos·AgF-Catalyzed 1,3-Dipolar Cycloaddition.

    PubMed

    Cayuelas, Alberto; Ortiz, Ricardo; Nájera, Carmen; Sansano, José M; Larrañaga, Olatz; de Cózar, Abel; Cossío, Fernando P

    2016-06-17

    The synthesis of constrained spirocycles is achieved effectively by means of 1,3-dipolar cyclodditions employing α-imino γ-lactones as azomethine ylide precursors and nitroalkenes as dipolarophiles. The complex formed by (R,R)-Me-DuPhos 18 and AgF is the most efficient bifunctional catalyst. Final spiro-nitroprolinates cycloadducts are obtained in good to moderate yields and both high diastereo- and enantioselectivities. Density functional theory (DFT) calculations supported the expected absolute configuration as well as other stereochemical parameters.

  16. General approach to glycosidase inhibitors. Enantioselective synthesis of deoxymannojirimycin and swainsonine.

    PubMed

    Martín, Rubén; Murruzzu, Caterina; Pericàs, Miquel A; Riera, Antoni

    2005-03-18

    [reaction: see text] Deoxymannojirimycin (2) and swainsonine (4) have been synthesized from each enantiomer of the same bicyclic carbamate precursor 7. The key intermediate was prepared by a simple and efficient three-step synthesis involving RCM of the diene 8, which in turn is easily accessible in any configuration from enantiomerically enriched 2,3-epoxy-4-penten-1-ol 9.

  17. Enantioselective Synthesis of Four Stereoisomers of Sulfinyl Ferrocenyl Quinones with Central, Planar, and Helical Chirality.

    PubMed

    del Hoyo, Ana M; Urbano, Antonio; Carreño, M Carmen

    2016-01-01

    Four stereoisomers of sulfinyl ferrocenyl-substituted helicenequinones having central, planar, and helical elements of chirality were stereoselectively formed, in one step, from reaction between enantiopure sulfinyl ferrocenyl dienes and a sulfinyl quinone. Asymmetric synthesis, kinetic resolution, or chemical resolution processes occurred in sequential cycloaddition, sulfoxide elimination, and partial aromatization steps.

  18. A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

    PubMed Central

    Zahel, Martin

    2013-01-01

    Summary (−)-Oxyphyllol was prepared in only 4 steps from an epoxy enone that already served as an intermediate for the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. PMID:24204414

  19. Enantioselective synthesis of α-aminosilanes by copper-catalyzed hydroamination of vinylsilanes.

    PubMed

    Niljianskul, Nootaree; Zhu, Shaolin; Buchwald, Stephen L

    2015-01-26

    The synthesis of α-aminosilanes by a highly enantio- and regioselective copper-catalyzed hydroamination of vinylsilanes is reported. The system employs Cu-DTBM-SEGPHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O-benzoylhydroxylamines as the electrophilic nitrogen source. This hydroamination reaction is compatible with differentially substituted vinylsilanes, thus providing access to amino acid mimics and other valuable chiral organosilicon compounds.

  20. Enantioselective synthesis of α-aminosilanes by copper-catalyzed hydroamination of vinylsilanes.

    PubMed

    Niljianskul, Nootaree; Zhu, Shaolin; Buchwald, Stephen L

    2015-01-26

    The synthesis of α-aminosilanes by a highly enantio- and regioselective copper-catalyzed hydroamination of vinylsilanes is reported. The system employs Cu-DTBM-SEGPHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O-benzoylhydroxylamines as the electrophilic nitrogen source. This hydroamination reaction is compatible with differentially substituted vinylsilanes, thus providing access to amino acid mimics and other valuable chiral organosilicon compounds. PMID:25475991

  1. Enantioselective Synthesis of α-Aminosilanes by Copper-Catalyzed Hydroamination of Vinylsilanes**

    PubMed Central

    Niljianskul, Nootaree; Zhu, Shaolin; Buchwald, Stephen L.

    2015-01-01

    The synthesis of α-aminosilanes by a highly enantio- and regioselective copper-catalyzed hydroamination of vinylsilanes is reported. The system employs Cu-DTBM-SEG-PHOS as the catalyst, diethoxymethylsilane as the stoichiometric reductant, and O-benzoylhydroxylamines as the electrophilic nitrogen source. This hydroamination reaction is compatible with differentially substituted vinylsilanes, thus providing access to amino acid mimics and other valuable chiral organosilicon compounds. PMID:25475991

  2. Chiral Brønsted Base-Promoted Nitroalkane Alkylation: Enantioselective Synthesis of sec-Alkyl-3-Substituted Indoles

    PubMed Central

    Dobish, Mark C.; Johnston, Jeffrey N.

    2010-01-01

    A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base. PMID:21090654

  3. Chiral fluorinated α-sulfonyl carbanions: enantioselective synthesis and electrophilic capture, racemization dynamics, and structure.

    PubMed

    Hellmann, Gunther; Hack, Achim; Thiemermann, Eric; Luche, Olaf; Raabe, Gerhard; Gais, Hans-Joachim

    2013-03-18

    Enantiomerically pure triflones R(1) CH(R(2) )SO2 CF3 have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF3 Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF3 SSCF3 . The deprotonation of RCH(Me)SO2 CF3 (R=CH2 Ph, iHex) with nBuLi with the formation of salts [RC(Me)SO2 CF3 ]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO2 CF3 group of (S)-MeOCH2 C(Me)(CH2 Ph)SO2 CF3 (95 % ee) by an ethyl group through the reaction with AlEt3 gave alkane MeOCH2 C(Me)(CH2 Ph)Et of 96 % ee. Racemization of salts [R(1) C(R(2) )SO2 CF3 ]Li follows first-order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a Cα S bond rotation as the rate-determining step. Lithium α-(S)-trifluoromethyl- and α-(S)-nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α-(S)-tert-butylsulfonyl carbanion salts. Whereas [PhCH2 C(Me)SO2 tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half-life of racemization at -105 °C of 2.4 h, that of [PhCH2 C(Me)SO2 CF3 ]Li at -78 °C is 30 d. DNMR spectroscopy of amides (PhCH2 )2 NSO2 CF3 and (PhCH2 )N(Ph)SO2 CF3 gave NS rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH2 C(Ph)SO2 R]M (M=Li, K, NBu4 ; R=CF3 , tBu) shows for both salts a confinement of the negative charge mainly to the Cα atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH2 C(Ph)SO2 CF3 ]Li⋅L}2 (L=2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH2 C(Ph)SO2 CF3 ]NBu4 have

  4. Palladium(II)-Catalyzed Enantioselective Synthesis of α-(Trifluoromethyl)arylmethylamines.

    PubMed

    Johnson, Thomas; Luo, Bo; Lautens, Mark

    2016-06-17

    We describe a method for the synthesis of α-(trifluoromethyl)arylmethylamines that consists of the palladium(II)-catalyzed addition of arylboroxines to imines derived from trifluoroacetaldehyde. Palladium acetate is used as a catalyst with electron-neutral or electron-rich arylboroxines, and it was found that addition of an ammonium or silver salt was crucial to promote the reaction of electron-poor boroxines. With (S)-t-Bu-PyOX as the chiral ligand, this method delivers a variety of α-trifluoromethylated amines in 57-91% yield and with greater than 92% ee in most cases. PMID:27246788

  5. Biocatalytic synthesis of C3 chiral building blocks by chloroperoxidase-catalyzed enantioselective halo-hydroxylation and epoxidation in the presence of ionic liquids.

    PubMed

    Liu, Yan; Wang, Yali; Jiang, Yucheng; Hu, Mancheng; Li, Shuni; Zhai, Quanguo

    2015-01-01

    The optically active C3 synthetic blocks are remarkably versatile intermediates for the synthesis of numerous pharmaceuticals and agrochemicals. This work provides a simple and efficient enzymatic synthetic route for the environment-friendly synthesis of C3 chiral building blocks. Chloroperoxidase (CPO)-catalyzed enantioselective halo-hydroxylation and epoxidation of chloropropene and allyl alcohol was employed to prepare C3 chiral building blocks in this work, including (R)-2,3-dichloro-1-propanol (DCP*), (R)-2,3-epoxy-1-propanol (GLD*), and (R)-3-chloro-1-2-propanediol (CPD*). The ee values of the formed C3 chiral building blocks DCP*, CPD*, and glycidol were 98.1, 97.5, and 96.7%, respectively. Moreover, the use of small amount of imidazolium ionic liquid enhanced the yield efficiently due to the increase of solubility of hydrophobic organic substrates in aqueous reaction media, as well as the improvement of affinity and selectivity of CPO to substrate.

  6. Diastereo- and enantioselective synthesis of organometallic bis(helicene)s by a combination of C-H activation and dynamic isomerization.

    PubMed

    Shen, Chengshuo; Anger, Emmanuel; Srebro, Monika; Vanthuyne, Nicolas; Toupet, Loïc; Roussel, Christian; Autschbach, Jochen; Réau, Régis; Crassous, Jeanne

    2013-12-01

    Homochiral and heterochiral cis-bis-cycloplatinated-[6]helicene derivatives 1b(1,2), as representative examples of platina[6]helicenes that share a common platinum center, have been prepared. A diastereo- and enantioselective synthesis, which combines CH activation and dynamic isomerization from heterochiral structure 1b(2) into homochiral structure 1b(1), is also described. Overall, this isomerization process results in the transfer of chiral information from one helicene moiety to the other one. The chiroptical properties of homochiral (P)- and (M)-1b(1) were greatly modified upon oxidation into their corresponding (P)- and (M)-diiodo-Pt(IV) complexes (5). The changes were also analyzed by performing theoretical calculations. C-H activation in the synthesis of organometallic helicenes is further demonstrated by the preparation of cis-bis-cycloplatinated-[8]helicene 1c. PMID:24173674

  7. Formal Synthesis of Solanoeclepin A: Enantioselective Allene Diboration and Intramolecular [2+2] Photocycloaddition for the Construction of the Tricyclic Core.

    PubMed

    Kleinnijenhuis, Roel A; Timmer, Brian J J; Lutteke, Ginger; Smits, Jan M M; de Gelder, René; van Maarseveen, Jan H; Hiemstra, Henk

    2016-01-22

    An enantioselective synthesis of an intermediate in the Tanino total synthesis of solanoeclepin A has been developed. The key step was an intramolecular [2+2] photocycloaddition, which led to the tricyclo[5.2.1.0(1, 6)] decane core in six steps. The first photosubstrate, prepared through an indium-mediated Barbier-type reaction, gave an excellent [2+2] cycloaddition, but it could not be obtained in sufficient enantiopurity. The second photosubstrate, prepared through an asymmetric allene diborylation in high enantiomeric excess, gave the [2+2] cycloaddition product in high yield on irradiation at 365 nm on 20 g scale in a flow system. Other important steps were the replacement of a boronate group at the quaternary carbon by a vinyl group and diastereoselective cyclopropanation of an allylic alcohol.

  8. Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations.

    PubMed

    Nicolaou, K C; Wang, Yanping; Lu, Min; Mandal, Debashis; Pattanayak, Manas R; Yu, Ruocheng; Shah, Akshay A; Chen, Jason S; Zhang, Hongjun; Crawford, James J; Pasunoori, Laxman; Poudel, Yam B; Chowdari, Naidu S; Pan, Chin; Nazeer, Ayesha; Gangwar, Sanjeev; Vite, Gregory; Pitsinos, Emmanuel N

    2016-07-01

    From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy. PMID:27266267

  9. Highly efficient molybdenum-based catalysts for enantioselective alkene metathesis

    PubMed Central

    Malcolmson, Steven J.; Meek, Simon J.; Sattely, Elizabeth S.; Schrock, Richard R.; Hoveyda, Amir H.

    2009-01-01

    Discovery of efficient catalysts is one of the most compelling objectives of modern chemistry. Chiral catalysts are in particularly high demand, as they facilitate synthesis of enantiomerically enriched small molecules that are critical to developments in medicine, biology and materials science1. Especially noteworthy are catalysts that promote—with otherwise inaccessible efficiency and selectivity levels—reactions demonstrated to be of great utility in chemical synthesis. Here we report a class of chiral catalysts that initiate alkene metathesis1 with very high efficiency and enantioselectivity. Such attributes arise from structural fluxionality of the chiral catalysts and the central role that enhanced electronic factors have in the catalytic cycle. The new catalysts have a stereogenic metal centre and carry only monodentate ligands; the molybdenum-based complexes are prepared stereoselectively by a ligand exchange process involving an enantiomerically pure aryloxide, a class of ligands scarcely used in enantioselective catalysis2,3. We demonstrate the application of the new catalysts in an enantioselective synthesis of the Aspidosperma alkaloid, quebrachamine, through an alkene metathesis reaction that cannot be promoted by any of the previously reported chiral catalysts. PMID:19011612

  10. Synthesis of ferrocene derivatives with planar chirality via palladium-catalyzed enantioselective C-H bond activation.

    PubMed

    Pi, Chao; Cui, Xiuling; Liu, Xiuyan; Guo, Mengxing; Zhang, Hanyu; Wu, Yangjie

    2014-10-01

    The first catalytic and enantioselective C-H direct acylation of ferrocene derivatives has been developed. A series of 2-acyl-1-dimethylaminomethylferrocenes with planar chirality were provided under highly efficient and concise one-pot conditions with up to 85% yield and 98% ee. The products obtained could be easily converted to various chiral ligands via diverse transformations.

  11. Enantioselective synthesis of both enantiomers of methyl dihydrojasmonate using solid-liquid asymmetric phase-transfer catalysis.

    PubMed

    Perrard, T; Plaquevent, J C; Desmurs, J R; Hébrault, D

    2000-09-21

    Both enantiomers of methyl dihydrojasmonate (-)-1 and (+)-1 were obtained by a short route using asymmetric Michael addition of dimethyl malonate onto pentyl enone 3, followed by nonracemizing demethoxycarbonylation. The key enantioselective step involves a new system of asymmetric solid-liquid phase-transfer catalysis using solvent-free conditions. Enantiomeric excess as high as 90% (91% yield) was achieved.

  12. Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross-metathesis-intramolecular oxo-Michael reaction.

    PubMed

    Zhang, Jun-Wei; Cai, Quan; Gu, Qing; Shi, Xiao-Xin; You, Shu-Li

    2013-09-11

    Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho-allylphenols and enones to provide a variety of benzofuran and benzoxazine derivatives in moderate to good yields and enantioselectivity. PMID:23884172

  13. Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross-metathesis-intramolecular oxo-Michael reaction.

    PubMed

    Zhang, Jun-Wei; Cai, Quan; Gu, Qing; Shi, Xiao-Xin; You, Shu-Li

    2013-09-11

    Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho-allylphenols and enones to provide a variety of benzofuran and benzoxazine derivatives in moderate to good yields and enantioselectivity.

  14. Enantioselective synthesis of 4-substituted tetrahydroisoquinolines via palladium-catalyzed intramolecular Friedel-Crafts type allylic alkylation of phenols.

    PubMed

    Zhao, Zheng-Le; Xu, Qing-Long; Gu, Qing; Wu, Xin-Yan; You, Shu-Li

    2015-03-14

    Palladium-catalyzed asymmetric intramolecular Friedel-Crafts type allylic alkylation reaction of phenols was developed under mild conditions. In the presence of Pd2(dba)3 with (1R,2R)-DACH-phenyl Trost ligand (L2) in toluene at 50 °C, the reaction provides various C4 substituted tetrahydroisoquinolines with moderate to excellent yields, regioselectivity and enantioselectivity. PMID:25625805

  15. New chiral derivatives of xanthones: synthesis and investigation of enantioselectivity as inhibitors of growth of human tumor cell lines.

    PubMed

    Fernandes, Carla; Masawang, Kamonporn; Tiritan, Maria Elizabeth; Sousa, Emília; de Lima, Virgínia; Afonso, Carlos; Bousbaa, Hassan; Sudprasert, Wanwisa; Pedro, Madalena; Pinto, Madalena M

    2014-02-01

    A highly efficient and practical methodology for synthesis of new chiral derivatives of xanthones (CDXs) in enantiomerically pure form has been developed. According to this approach, thirty CDXs (3-32) were synthesized by coupling a carboxyxanthone (1) and a carboxymethoxyxanthone (2) with both enantiomers of commercially available chiral building blocks, namely six amino alcohols, one amine and one amino ester. The activation of the carboxylic acid group of the xanthonic scaffold was carried out with the coupling reagent O-(benzotriazol-1-yl)-N-N-N'-N'-tetramethyluronium tetrafluoroborate (TBTU), in the presence of a catalytic amount of TEA in anhydrous THF. The coupling reactions with the chiral blocks were performed at room temperature with short reactions times, excellent yields (ranging from 94% to 99%), and very high enantiomeric excess. The synthesized CDXs were evaluated for their effect on the in vitro growth of three human tumor cell lines, namely A375-C5 (melanoma), MCF-7 (breast adenocarcinoma), and NCI-H460 (non-small cell lung cancer). The most active compound was CDX 15 being active in all human tumor cell lines with values of GI50 of 32.15±2.03μM for A375-C5, 22.55±1.99μM for MCF-7, and 14.05±1.82μM for NCI-H460. Nevertheless, some CDXs showed cell-type selectivity. Furthermore, the growth inhibitory effects, in some cases, demonstrated to be depending on the stereochemistry of the CDXs. An interesting example was observed with the enantiomers 3 and 4, which demonstrated high enantioselectivity for MCF-7 and NCI-H460 cell lines. It can be inferred that the effects on the growth of the human tumor cell lines can be ascribed not only to the nature and positions of substituents on the xanthonic scaffold but also to the stereochemistry of the CDXs. Some considerations regarding structure-activity relationship within this class of compounds will be highlighted. PMID:24411197

  16. Enantioselective tandem reaction of chromone-derived Morita-Baylis-Hillman carbonates with benzylamines catalyzed by a trifunctional organocatalyst: the synthesis of chiral 3-aminomethylene-flavanones.

    PubMed

    Zhong, Neng-jun; Liu, Li; Wang, Dong; Chen, Yong-Jun

    2013-05-01

    An enantioselective tandem reaction of chromones-derived MBH carbonates (1) with benzylamines (2) catalyzed by a trifunctional organocatalyst, cinchonidine-amide-thiourea, has been developed in moderate to good yields (50-87%) and enantioselectivities (up to 89% ee).

  17. Synthetic applications of enantioselective protonation and case study for (S)-alpha-damascone.

    PubMed

    Fehr, Charles; Randall, Harvey

    2008-06-01

    Among the fragrance compounds synthesized by enantioselective protonation, (S)-alpha-damascone, (R)-muscone, and (S,S)-Vulcanolide are the most prominent ones. (S)-alpha-damascone has been prepared by four different procedures: from the magnesium enolate, from the lithium enolate, from the enol, and from the corresponding thiol ester. We now present a new, industrially viable protocol for the addition of allyl magnesium chloride to the 'cyclogeranoketene' by a Barbier reaction, followed by protonation of the ensuing magnesium enolate by an aggregate formed from (-)-N-isopropylephedrine, lithium isopropylate, and acetic acid, furnishing (S)-alpha-damascone in 91% yield and with 71% ee.

  18. Structure determination of bisacetylenic oxylipins in carrots (Daucus carota L.) and enantioselective synthesis of falcarindiol.

    PubMed

    Schmiech, Ludger; Alayrac, Carole; Witulski, Bernhard; Hofmann, Thomas

    2009-11-25

    Although bisacetylenic oxylipins have been demonstrated to exhibit diverse biological activities, the chemical structures of many representatives of this class of phytochemicals still remain elusive. As carrots play an important role in our daily diet and are known as a source of bisacetylenes, an extract made from Daucus carota L. was screened for bisacetylenic oxylipins, and, after isolation, their structures were determined by means of LC-MS and 1D/2D NMR spectroscopy. Besides the previously reported falcarinol, falcarindiol, and falcarindiol 3-acetate, nine additional bisacetylenes were identified, among which six derivatives are reported for the first time in literature and three compounds were previously not identified in carrots. To determine the absolute stereochemistry of falcarindiol in carrots, the (3R,8R)-, (3R,8S)-, (3S,8R)-, and (3S,8S)-stereoisomers of falcarindiol were synthesized according to a novel 10-step total synthesis involving a Cadiot-Chodkiewicz cross-coupling reaction of (S)- and (R)-trimethylsilanyl-4-dodecen-1-yn-3-ol and (R)- and (S)-5-bromo-1-penten-4-yn-3-ol, respectively. Comparative chiral HPLC analysis of the synthetic stereoisomers with the isolated phytochemical led to the unequivocal assignment of the (Z)-(3R,8S)-configuration for falcarindiol in carrot extracts from Daucus carota L.

  19. Enantioselective Synthesis of Vicinal (R,R)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase

    PubMed Central

    Calam, Eduard; González-Roca, Eva; Fernández, M. Rosario; Dequin, Sylvie; Parés, Xavier; Virgili, Albert

    2016-01-01

    Butanediol dehydrogenase (Bdh1p) from Saccharomyces cerevisiae belongs to the superfamily of the medium-chain dehydrogenases and reductases and converts reversibly R-acetoin and S-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol, respectively. It is specific for NAD(H) as a coenzyme, and it is the main enzyme involved in the last metabolic step leading to (2R,3R)-2,3-butanediol in yeast. In this study, we have used the activity of Bdh1p in different forms—purified enzyme, yeast extracts, permeabilized yeast cells, and as a fusion protein (with yeast formate dehydrogenase, Fdh1p)—to transform several vicinal diketones to the corresponding diols. We have also developed a new variant of the delitto perfetto methodology to place BDH1 under the control of the GAL1 promoter, resulting in a yeast strain that overexpresses butanediol dehydrogenase and formate dehydrogenase activities in the presence of galactose and regenerates NADH in the presence of formate. While the use of purified Bdh1p allows the synthesis of enantiopure (2R,3R)-2,3-butanediol, (2R,3R)-2,3-pentanediol, (2R,3R)-2,3-hexanediol, and (3R,4R)-3,4-hexanediol, the use of the engineered strain (as an extract or as permeabilized cells) yields mixtures of the diols. The production of pure diol stereoisomers has also been achieved by means of a chimeric fusion protein combining Fdh1p and Bdh1p. Finally, we have determined the selectivity of Bdh1p toward the oxidation/reduction of the hydroxyl/ketone groups from (2R,3R)-2,3-pentanediol/2,3-pentanedione and (2R,3R)-2,3-hexanediol/2,3-hexanedione. In conclusion, Bdh1p is an enzyme with biotechnological interest that can be used to synthesize chiral building blocks. A scheme of the favored pathway with the corresponding intermediates is proposed for the Bdh1p reaction. PMID:26729717

  20. Enantioselective Synthesis of Vicinal (R,R)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase.

    PubMed

    Calam, Eduard; González-Roca, Eva; Fernández, M Rosario; Dequin, Sylvie; Parés, Xavier; Virgili, Albert; Biosca, Josep A

    2016-03-01

    Butanediol dehydrogenase (Bdh1p) from Saccharomyces cerevisiae belongs to the superfamily of the medium-chain dehydrogenases and reductases and converts reversibly R-acetoin and S-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol, respectively. It is specific for NAD(H) as a coenzyme, and it is the main enzyme involved in the last metabolic step leading to (2R,3R)-2,3-butanediol in yeast. In this study, we have used the activity of Bdh1p in different forms-purified enzyme, yeast extracts, permeabilized yeast cells, and as a fusion protein (with yeast formate dehydrogenase, Fdh1p)-to transform several vicinal diketones to the corresponding diols. We have also developed a new variant of the delitto perfetto methodology to place BDH1 under the control of the GAL1 promoter, resulting in a yeast strain that overexpresses butanediol dehydrogenase and formate dehydrogenase activities in the presence of galactose and regenerates NADH in the presence of formate. While the use of purified Bdh1p allows the synthesis of enantiopure (2R,3R)-2,3-butanediol, (2R,3R)-2,3-pentanediol, (2R,3R)-2,3-hexanediol, and (3R,4R)-3,4-hexanediol, the use of the engineered strain (as an extract or as permeabilized cells) yields mixtures of the diols. The production of pure diol stereoisomers has also been achieved by means of a chimeric fusion protein combining Fdh1p and Bdh1p. Finally, we have determined the selectivity of Bdh1p toward the oxidation/reduction of the hydroxyl/ketone groups from (2R,3R)-2,3-pentanediol/2,3-pentanedione and (2R,3R)-2,3-hexanediol/2,3-hexanedione. In conclusion, Bdh1p is an enzyme with biotechnological interest that can be used to synthesize chiral building blocks. A scheme of the favored pathway with the corresponding intermediates is proposed for the Bdh1p reaction.

  1. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions

    NASA Astrophysics Data System (ADS)

    Lee, Kyunga; Silverio, Daniel L.; Torker, Sebastian; Robbins, Daniel W.; Haeffner, Fredrik; van der Mei, Farid W.; Hoveyda, Amir H.

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium–organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.

  2. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions.

    PubMed

    Lee, KyungA; Silverio, Daniel L; Torker, Sebastian; Robbins, Daniel W; Haeffner, Fredrik; van der Mei, Farid W; Hoveyda, Amir H

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.

  3. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions.

    PubMed

    Lee, KyungA; Silverio, Daniel L; Torker, Sebastian; Robbins, Daniel W; Haeffner, Fredrik; van der Mei, Farid W; Hoveyda, Amir H

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities. PMID:27442282

  4. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions

    NASA Astrophysics Data System (ADS)

    Lee, Kyunga; Silverio, Daniel L.; Torker, Sebastian; Robbins, Daniel W.; Haeffner, Fredrik; van der Mei, Farid W.; Hoveyda, Amir H.

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.

  5. A homochiral metal-organic porous material for enantioselective separation and catalysis

    NASA Astrophysics Data System (ADS)

    Seo, Jung Soo; Whang, Dongmok; Lee, Hyoyoung; Jun, Sung Im; Oh, Jinho; Jeon, Young Jin; Kim, Kimoon

    2000-04-01

    Inorganic zeolites are used for many practical applications that exploit the microporosity intrinsic to their crystal structures. Organic analogues, which are assembled from modular organic building blocks linked through non-covalent interactions, are of interest for similar applications. These range from catalysis, separation and sensor technology to optoelectronics, with enantioselective separation and catalysis being especially important for the chemical and pharmaceutical industries. The modular construction of these analogues allows flexible and rational design, as both the architecture and chemical functionality of the micropores can, in principle, be precisely controlled. Porous organic solids with large voids and high framework stability have been produced, and investigations into the range of accessible pore functionalities have been initiated. For example, catalytically active organic zeolite analogues are known, as are chiral metal-organic open-framework materials. However, the latter are only available as racemic mixtures, or lack the degree of framework stability or void space that is required for practical applications. Here we report the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Our synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.

  6. N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes.

    PubMed

    Shi, Ying; Jung, Byunghyuck; Torker, Sebastian; Hoveyda, Amir H

    2015-07-22

    The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes. PMID:26172476

  7. N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes.

    PubMed

    Shi, Ying; Jung, Byunghyuck; Torker, Sebastian; Hoveyda, Amir H

    2015-07-22

    The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.

  8. Highly enantioselective synthesis of γ-substituted butenolides via the vinylogous Mukaiyama-Michael reaction catalyzed by a chiral scandium(III)-N,N'-dioxide complex.

    PubMed

    Zhang, Qi; Xiao, Xiao; Lin, Lili; Liu, Xiaohua; Feng, Xiaoming

    2011-08-21

    A highly efficient catalytic asymmetric vinylogous Mukaiyama-Michael reaction of the 2-silyloxyfuran with chalcone derivatives, catalyzed by a chiral N,N'-dioxide-scandium(III) complex, has been accomplished which tolerates a wide range of substrates. The reaction proceeds with complete regioselectivities, excellent diastereoselectivities (up to >99 : 1 dr) and good to excellent enantioselectivities (up to 94% ee) under mild conditions, delivering highly functionalized enantiomerically enriched anti-γ-substituted butenolides. The process is air-tolerant and easily manipulated with available reagents. In order to illustrate the synthetic potential of this reaction, the gram-scale synthesis and the elaboration of the butenolides have been explored. On the basis of the experimental results, a possible catalytic cycle and favorable stereorecognition model have been proposed.

  9. Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.

    PubMed

    Alonso, Beatriz; Ocejo, Marta; Carrillo, Luisa; Vicario, Jose L; Reyes, Efraim; Uria, Uxue

    2013-01-18

    We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.

  10. Cloning and Characterization of a Novel Esterase from Rhodococcus sp. for Highly Enantioselective Synthesis of a Chiral Cilastatin Precursor

    PubMed Central

    Zhang, Yan; Pan, Jiang; Luan, Zheng-Jiao; Park, Sunghoon

    2014-01-01

    A novel nonheme chloroperoxidase (RhEst1), with promiscuous esterase activity for enantioselective hydrolysis of ethyl (S)-2,2-dimethylcyclopropanecarboxylate, was identified from a shotgun library of Rhodococcus sp. strain ECU1013. RhEst1 was overexpressed in Escherichia coli BL21(DE3), purified to homogeneity, and functionally characterized. Fingerprinting analysis revealed that RhEst1 prefers para-nitrophenyl (pNP) esters of short-chain acyl groups. pNP esters with a cyclic acyl moiety, especially that with a cyclobutanyl group, were also substrates for RhEst1. The Km values for methyl 2,2-dimethylcyclopropanecarboxylate (DmCpCm) and ethyl 2,2-dimethylcyclopropane carboxylate (DmCpCe) were 0.25 and 0.43 mM, respectively. RhEst1 could serve as an efficient hydrolase for the bioproduction of optically pure (S)-2,2-dimethyl cyclopropane carboxylic acid (DmCpCa), which is an important chiral building block for cilastatin. As much as 0.5 M DmCpCe was enantioselectively hydrolyzed into (S)-DmCpCa, with a molar yield of 47.8% and an enantiomeric excess (ee) of 97.5%, indicating an extremely high enantioselectivity (E = 240) of this novel and unique biocatalyst for green manufacturing of highly valuable chiral chemicals. PMID:25239898

  11. Enantioselective Vinylogous Organocascade Reactions.

    PubMed

    Hepburn, Hamish B; Dell'Amico, Luca; Melchiorre, Paolo

    2016-08-01

    Cascade reactions are powerful tools for rapidly assembling complex molecular architectures from readily available starting materials in a single synthetic operation. Their marriage with asymmetric organocatalysis has led to the development of novel techniques, which are now recognized as reliable strategies for the one-pot enantioselective synthesis of stereochemically dense molecules. In recent years, even more complex synthetic challenges have been addressed by applying the principle of vinylogy to the realm of organocascade catalysis. The key to the success of vinylogous organocascade reactions is the unique ability of the chiral organocatalyst to transfer reactivity to a distal position without losing control on the stereo-determining events. This approach has greatly expanded the synthetic horizons of the field by providing the possibility of forging multiple stereocenters in remote positions from the catalyst's point of action with high selectivity, while simultaneously constructing multiple new bonds. This article critically describes the developments achieved in the field of enantioselective vinylogous organocascade reactions, charting the ideas, the conceptual advances, and the milestone reactions that have been essential for reaching highly practical levels of synthetic efficiency. PMID:27256039

  12. Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

    NASA Astrophysics Data System (ADS)

    Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

    Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

  13. Enantioselective analysis of 4-hydroxycyclophosphamide in human plasma with application to a clinical pharmacokinetic study.

    PubMed

    de Castro, Francine Attié; Scatena, Gabriel dos Santos; Rocha, Otávio Pelegrino; Marques, Maria Paula; Cass, Quézia Bezerra; Simões, Belinda Pinto; Lanchote, Vera Lucia

    2016-02-01

    Cyclophosphamide (CY) is one of the most common immunosuppressive agents used in autologous hematopoietic stem cell transplantation. CY is a prodrug and is metabolized to active 4-hydroxycyclophosphamide (HCY). Many authors have suggested an association between enantioselectivity in CY metabolism and treatment efficacy and/or complications. This study describes the development and validation of an analytical method of HCY enantiomers in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) that can be applied to pharmacokinetic studies, filling this gap in the literature. HCY enantiomers previously derivatized with phenylhydrazine were extracted from 200-μL plasma aliquots spiked with antipyrine as internal standard and a mixture of hexane and dichloromethane (80:20, v/v) was used as the extraction solvent. The derivatized HCY enantiomers were resolved on a Chiracel(®) OD-R column using water:acetonitrile:formic acid (55:45:0.2, v/v) as the mobile phase. No matrix effect was observed and the analysis of HCY enantiomers was linear for plasma concentrations of 5-5000ng of each enantiomer/mL plasma. The coefficients of variation and inaccuracy calculated in precision and accuracy assessments were less than 15%. HCY was stable in human plasma after three successive freeze/thaw cycles, during 3h at room temperature, and in the autosampler at 4°C for 24h after processing, with deviation values less than 15%. The method was applied to evaluate the kinetic disposition of HCY in a patient with multiple sclerosis who was pretreated with intravenous racemic CY for stem cell transplantation. The clinical study showed enantioselectivity in the pharmacokinetics of HCY.

  14. Straightforward methodology for the enantioselective synthesis of benzo[a]- and indolo[2,3-a]quinolizidines.

    PubMed

    Amat, Mercedes; Santos, Maria M M; Bassas, Oriol; Llor, Núria; Escolano, Carmen; Gómez-Esqué, Arantxa; Molins, Elies; Allin, Steven M; McKee, Vickie; Bosch, Joan

    2007-07-01

    An enantioselective two-step route to substituted benzo[a]- and indolo[2,3-a]quinolizidines has been developed. It consists of (i) a stereoselective cyclocondensation of a racemic or prochiral delta-oxo(di)ester with either (S)-(3,4-dimethoxyphenyl)alaninol or (S)-tryptophanol in a process involving a dynamic kinetic resolution and/or the differentiation of enantiotopic or diastereotopic ester groups, and (ii) a subsequent stereocontrolled cyclization on the aromatic ring taking advantage of the masked N-acyl iminium ion present in the resulting oxazolopiperidone lactams. PMID:17547461

  15. Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs.

    PubMed

    Zhang, Qiuyang; Yang, Wei; Zhang, Qing; Yang, Yue; Li, Junxiu; Lu, Yang; Zheng, Yi; He, Jiake; Zhao, Di; Chen, Xijing

    2015-07-01

    An enantioselective high-performance liquid chromatography method was developed and validated for the determination of oxiracetam enantiomers, a cognition and memory enhancer, in beagle dog plasma. The plasma samples were prepared by methanol extraction from 200μL plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250mm×4.6mm, 5μm) with mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0mL/min. The column elute was monitored using ultraviolet detection at 214nm. The method was linear over concentration range 0.50-100μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.78-13.61 and 0.74-8.92% for (R)- and (S)-oxiracetam, respectively. The relative error values of accuracy ranged from -4.74 to 10.48% for (R)-oxiracetam and from -0.19 to 11.48% for (S)-oxiracetam. The method was successfully applied to a pharmacokinetic study of individual enantiomer and racemic oxiracetam in beagle dogs after oral administration. The disposition of the two enantiomers was not stereoselective and chiral inversion was not observed in beagle dogs. The pharmacokinetic profiles of (S)-oxiracetam were similar with racemic oxiracetam in beagle dogs.

  16. Concise Enantioselective Synthesis of Oxygenated Steroids via Sequential Copper(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions.

    PubMed

    Cichowicz, Nathan R; Kaplan, Will; Khomutnyk, Yaroslav; Bhattarai, Bijay; Sun, Zhankui; Nagorny, Pavel

    2015-11-18

    A new scalable enantioselective approach to functionalized oxygenated steroids is described. This strategy is based on chiral bis(oxazoline) copper(II) complex-catalyzed enantioselective and diastereoselective Michael reactions of cyclic ketoesters and enones to install vicinal quaternary and tertiary stereocenters. In addition, the utility of copper(II) salts as highly active catalysts for the Michael reactions of traditionally unreactive β,β'-enones and substituted β,β'-ketoesters that results in unprecedented Michael adducts containing vicinal all-carbon quaternary centers is also demonstrated. The Michael adducts subsequently undergo base-promoted diastereoselective aldol cascade reactions resulting in the natural or unnatural steroid skeletons. The experimental and computational studies suggest that the torsional strain effects arising from the presence of the Δ(5)-unsaturation are key controlling elements for the formation of the natural cardenolide scaffold. The described method enables expedient generation of polycyclic molecules including modified steroidal scaffolds as well as challenging-to-synthesize Hajos-Parrish and Wieland-Miescher ketones.

  17. Concise Enantioselective Synthesis of Oxygenated Steroids via Sequential Copper(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions

    PubMed Central

    Cichowicz, Nathan R.; Kaplan, Will; Khomutnyk, Yaroslav; Bhattarai, Bijay; Sun, Zhankui; Nagorny, Pavel

    2015-01-01

    A new scalable enantioselective approach to functionalized oxygenated steroids is described. This strategy is based on chiral bis(oxazoline) copper(II) complex-catalyzed enantioselective and diastereoselective Michael reactions of cyclic ketoesters and enones to install vicinal quaternary and tertiary stereocenters. In addition, the utility of copper(II) salts as highly active catalysts for the Michael reactions of traditionally unreactive ββ′-enones and substituted ββ′-ketoesters that results in unprecedented Michael adducts containing vicinal all-carbon quaternary centers is also demonstrated. The Michael adducts subsequently undergo base-promoted diastereoselective aldol cascade reactions resulting in the natural or unnatural steroid skeletons. The experimental and computational studies suggest that the torsional strain effects arising from the presence of the Δ5-unsaturation are key controling elements for the formation of the natural cardenolide scaffold. The described method enables expedient generation of polycyclic molecules including modified steroidal scaffolds as well as challenging-to-synthesize Hajos-Parrish and Wieland-Miescher ketones. PMID:26491886

  18. Enantioselective analysis of triazole fungicide myclobutanil in cucumber and soil under different application modes by chiral liquid chromatography/tandem mass spectrometry.

    PubMed

    Dong, Fengshou; Cheng, Li; Liu, Xingang; Xu, Jun; Li, Jing; Li, Yuanbo; Kong, Zhiqiang; Jian, Qiu; Zheng, Yongquan

    2012-02-29

    A sensitive and enantioselective method was developed and validated for the determination of myclobutanil enantiomers by chiral liquid chromatography coupled with tandem mass spectrometry. The separation and determination were performed using reversed-phase chromatography on a Chiralcel OD-RH column, with ACN-water (70/30, v/v) as the mobile phase under isocratic conditions at 0.5 mL/min flow rate. The matrix effect, linearity, precision, accuracy, and stability were evaluated. The proposed method then was successfully applied to the study of enantioselective degradation of rac-myclobutanil in cucumber and soil under different application modes. The results showed that the preferential degradation of (+)-myclobutanil resulted in an enrichment of the (-)-myclobutanil residue in plant and soil. Moreover, in cucumber, the stereoselective intensity of myclobutanil under root douche treatment was stronger than that under foliar spraying treatment, whereas in soil, the intensity was exactly opposite. The probable reasons underlying these enantioselective effects were also discussed. This study highlighted the importance of examining the fate of both enantiomers in the greenhouse system for the correct use of chiral pesticides. PMID:22288843

  19. Copper-catalyzed propargylic substitution of dichloro substrates: enantioselective synthesis of trisubstituted allenes and formation of propargylic quaternary stereogenic centers.

    PubMed

    Li, Hailing; Grassi, David; Guénée, Laure; Bürgi, Thomas; Alexakis, Alexandre

    2014-12-01

    An easy and versatile Cu-catalyzed propargylic substitution process is presented. Using easily prepared prochiral dichloro substrates, readily available Grignard reagents together with catalytic amount of copper salt and chiral ligand, we accessed a range of synthetically interesting trisubstituted chloroallenes. Substrate scope and nucleophile scope are broad, providing generally high enantioselectivity for the desired 1,3-substitution products. The enantioenriched chloroallenes could be further transformed into the corresponding trisubstituted allenes or terminal alkynes bearing all-carbon quaternary stereogenic centers, through the copper-catalyzed enantiospecific 1,1/1,3-substitutions. The two successive copper-catalyzed reactions could be eventually combined into a one-pot procedure and different desired allenes or alkynes were obtained respectively with high enantiomeric excesses. PMID:25327947

  20. Ultrasound-mediated synthesis of camphoric acid-based chiral salens for the enantioselective trimethylsilylcyanation of aldehydes.

    PubMed

    Serra, Maria E Silva; Murtinho, Dina; Goth, Albertino; Rocha Gonsalves, António M D'A; Abreu, Paulo E; Pais, Alberto A C C

    2010-05-01

    New chiral salen ligands were prepared by the ultrasound-irradiated condensation of optically active (1R, 3S)-1,2,2-trimethyl-1,3-diaminocyclopentane with aromatic 1-hydroxyaldehydes. The ultrasound-mediated process is more convenient due to shorter reaction times, energy economy, and easier isolation of the products. The in situ formed Ti(IV)(salen) complexes, evaluated as catalysts in the enantioselective trimethylsilylcyanation of benzaldehyde, were found to be efficient for this process, originating the corresponding product in high yields (72-99%) and selectivities of up to 79%. The lowest energy transition states were determined by computational studies. These results were in qualitative agreement with the experimentally observed ones. PMID:19603482

  1. Magnetite: from synthesis to applications.

    PubMed

    Unsoy, Gozde; Gunduz, Ufuk; Oprea, Ovidiu; Ficai, Denisa; Sonmez, Maria; Radulescu, Marius; Alexie, Mihaela; Ficai, Anton

    2015-01-01

    In this review the synthesis, functionalization and some applications of magnetite nanoparticles (MNPs) were highlighted. It is our intention to highlight the correlations between the synthesis routes, related synthesis parameters, functionalization strategies and the properties expected for the materials containing MNPs. The uses of MNPs are strongly influenced by the properties of the materials. Therefore this review is trying to discuss the applications of the magnetite and magnetite based nanomaterials by taking into account all the factors that can influence the properties of the final materials and consequently their potential applications. PMID:25877083

  2. Enantioselective Synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine and their Racemization-free Incorporation into Oligopeptides via Solid-phase Synthesis

    PubMed Central

    Xiao, Nu; Jiang, Zhong-Xing; Yu, Y. Bruce

    2010-01-01

    An efficient method for the enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine (tfT) on multi-gram scales was developed. Absolute configurations of the two stereoisomers were ascertained by X-ray crystallography. Racemization-free coupling conditions for the incorporation of tfT into oligopeptides were then explored. For solution-phase synthesis, tfT racemization was not an issue under conventional coupling conditions. For solid-phase synthesis, the following conditions were identified to achieve racemization-free synthesis: if tfT (3.0 eq.) was not the first amino acid to be linked to the resin (1.0 eq.), the condition is: 2.7 eq. DIC/3.0 eq. HOBt as the coupling reagent at 0 °C for 20 h; if tfT (3.0 eq.) was the first amino acid to be linked to the resin (1.0 eq.), then 1.0 eq. of CuCl2 needs to be added to the coupling reagent. PMID:17702025

  3. Diastereoselective Synthesis of Tetrasubstituted Propargylamines via Hydroamination and Metalation of 1-Alkynes and Their Enantioselective Conversion to Trisubstituted Chiral Allenes.

    PubMed

    Periasamy, Mariappan; Reddy, Polimera Obula; Satyanarayana, Iddum; Mohan, Lakavathu; Edukondalu, Athukuri

    2016-02-01

    Reaction of cyclic secondary amines with 1-alkynes and copper(I) chloride at 110-120 °C gives the corresponding alkynylcopper complex, which adds to the iminium ion intermediate formed in situ by hydroamination of 1-alkynes to give the corresponding propargylamine derivatives in up to 94% yield and 99% regioselectivity. The diastereomerically pure chiral propargylamines were obtained in 23-89% yield using optically active 2-benzyl morpholine and N-methyl camphanyl piperazine. These chiral propargylamines are readily converted to the corresponding trisubstitued chiral allenes in 71-89% yields with up to 99% ee upon reaction with ZnBr2 at 120 °C. The results are discussed considering mechanisms involving diastereoselective addition of alkynylcopper complex formed in situ to iminium ions formed in situ regioselectively to produce the corresponding propargylamines, which in turn give the chiral allenes with very high enantioselectivity via an intramolecular 1,5-hydrogen shift in the presence of zinc bromide. PMID:26726072

  4. Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols.

    PubMed

    Yu, Feng; Zhou, Ji-Ning; Zhang, Xi-Chang; Sui, Yao-Zong; Wu, Fei-Fei; Xie, Lin-Jie; Chan, Albert S C; Wu, Jing

    2011-12-01

    In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively. PMID:22065457

  5. Copper-catalyzed enantioselective allylic substitution with alkylboranes.

    PubMed

    Shido, Yoshinori; Yoshida, Mika; Tanabe, Masahito; Ohmiya, Hirohisa; Sawamura, Masaya

    2012-11-14

    The first catalytic enantioselective allylic substitution reaction with alkylboron compounds has been achieved. The reaction between alkyl-9-BBN reagents and primary allylic chlorides proceeded with excellent γ-selectivities and high enantioselectivities under catalysis of a Cu(I)-DTBM-SEGPHOS system. The protocol produces terminal alkenes with an allylic stereogenic center branched with functionalized sp(3)-alkyl groups. The reaction with a γ-silicon-substituted allyl chloride affords an efficient strategy for the enantioselective synthesis of functionalized α-stereogenic chiral allylsilanes. PMID:23106350

  6. Catalytic enantioselective peroxidation of alpha,beta-unsaturated ketones.

    PubMed

    Lu, Xiaojie; Liu, Yan; Sun, Bingfeng; Cindric, Brittany; Deng, Li

    2008-07-01

    Despite the potential of chiral peroxides as biologically interesting or even clinically important compounds, no catalytic enantioselective peroxidation has been reported. With a chiral catalyst not only to induce enantioselectivity but also to convert a well established epoxidation pathway into a peroxidation pathway, the first efficient catalytic peroxidation has been successfully developed. Employing readily available alpha,beta-unsaturated ketones and hydroperoxides and an easily accessible cinchona alkaloid catalyst, this novel reaction will open new possibilities in the asymmetric synthesis of chiral peroxides. Under different conditions a highly enantioselective epoxidation with the same starting materials, reagents, and catalyst has was also established.

  7. Discovery, application and protein engineering of Baeyer-Villiger monooxygenases for organic synthesis.

    PubMed

    Balke, Kathleen; Kadow, Maria; Mallin, Hendrik; Sass, Stefan; Bornscheuer, Uwe T

    2012-08-21

    Baeyer-Villiger monooxygenases (BVMOs) are useful enzymes for organic synthesis as they enable the direct and highly regio- and stereoselective oxidation of ketones to esters or lactones simply with molecular oxygen. This contribution covers novel concepts such as searching in protein sequence databases using distinct motifs to discover new Baeyer-Villiger monooxygenases as well as high-throughput assays to facilitate protein engineering in order to improve BVMOs with respect to substrate range, enantioselectivity, thermostability and other properties. Recent examples for the application of BVMOs in synthetic organic synthesis illustrate the broad potential of these biocatalysts. Furthermore, methods to facilitate the more efficient use of BVMOs in organic synthesis by applying e.g. improved cofactor regeneration, substrate feed and in situ product removal or immobilization are covered in this perspective.

  8. Highly enantioselective synthesis of fluorinated gamma-amino alcohols through proline-catalyzed cross-Mannich reaction.

    PubMed

    Fustero, Santos; Jiménez, Diego; Sanz-Cervera, Juan F; Sánchez-Roselló, María; Esteban, Elisabet; Simón-Fuentes, Antonio

    2005-08-01

    A new, simple route for the synthesis of fluorinated beta-alkyl gamma-amino alcohols in optically pure form in only two steps and featuring proline catalysis from inexpensive and readily available starting materials is described. The applied strategy allows for the introduction of diversity into both the beta-fluoroalkyl and alpha-alkyl groups of these compounds. [reaction: see text

  9. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    PubMed Central

    Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

    2012-01-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

  10. Voice synthesis application

    NASA Astrophysics Data System (ADS)

    Lightstone, P. C.; Davidson, W. M.

    1982-01-01

    Selection of a speech synthesis system as an augmentation for a perimeter security device is described. Criteria used in selection of a system are discussed. The final system is a speech 1000 speech synthesizer board that has a 2000 word speech lexicon, a first time charge for a 32 K EPROM of custom words, and extra features such as an alternate command to adjust desired listening level.

  11. Voice synthesis application

    SciTech Connect

    Lightstone, P.C.; Davidson, W.M.

    1982-01-27

    Selection of a speech synthesis system as an augmentation for a perimeter security device is described. Criteria used in selection of a system are discussed. The final system is a speech 1000 speech synthesizer board that has a 2000 word speech lexicon, a first time charge of $75 for a 32 K EPROM of custom words, and extra features such as an alternate command to adjust desired listening level.

  12. Enantioselective catalysis using lanthanide Schiff base complexes

    SciTech Connect

    Watkin, J.G.

    1996-10-01

    The use of lanthanide-based catalysts to facilitate organic transformations is currently an area of rapid growth, in particular the application of lanthanide alkoxide and triflate derivatives as effective Lewis-acidic catalysts for Michael additions and aldol reactions, and bis-pentamethylcyclopentadienyl derivatives as extremely active catalysts for hydrogenation and enantioselective hydroamination reactions. We have begun an investigation into the use of lanthanide complexes containing chiral alkoxide ligands as Lewis-acidic catalysts for enantioselective organic reactions. Since the large ionic radii of the lanthanide +III metal centers can often lead to oligomerization of simple alkoxide species, we have also examined the use of multidentate, chelating Schiff base ligands to provide an asymmetric environment about a lanthanide metal center. Structural investigations of the catalysts will be described, together with the use of these catalysts in enantioselective Meerwein-Ponndorf-Verley reduction of ketones and nitroaldol reactions.

  13. Highly regio- and enantioselective synthesis of N-substituted 2-pyridones: iridium-catalyzed intermolecular asymmetric allylic amination.

    PubMed

    Zhang, Xiao; Yang, Ze-Peng; Huang, Lin; You, Shu-Li

    2015-02-01

    The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98% yield and 99% ee. PMID:25504907

  14. A Series of Cinchona-Derived N-Oxide Phase-Transfer Catalysts: Application to the Photo-Organocatalytic Enantioselective α-Hydroxylation of β-Dicarbonyl Compounds.

    PubMed

    Wang, Yakun; Yin, Hang; Tang, Xiaofei; Wu, Yufeng; Meng, Qingwei; Gao, Zhanxian

    2016-08-19

    A series of cinchona-derived N-oxide asymmetric phase-transfer catalysts were synthesized and applied in the enantioselective photo-organocatalytic α-hydroxylation of β-keto esters and β-keto amides (23 examples) using molecular oxygen in excellent yields (up to 98%) and high enantioselectivities (up to 83% ee). These new catalysts could be recycled and reused six times for such a reaction with almost the original reactivity and enantioselectivity. PMID:27336753

  15. Enantioselective synthesis of allenylenol silyl ethers via chiral lithium amide mediated reduction of ynenoyl silanes and their Diels-Alder reactions.

    PubMed

    Sasaki, Michiko; Kondo, Yasuhiro; Moto-ishi, Ta-ichi; Kawahata, Masatoshi; Yamaguchi, Kentaro; Takeda, Kei

    2015-03-01

    An enantioselective Meerwein-Ponndorf-Verley-type reduction of ynenoylsilanes by a chiral lithium amide followed by a Brook rearrangement and anti-mode protonation across conjugated 1,3-enynes provides allene derivatives bearing a 2-siloxyvinyl moiety in high enantioselectivity. The E/Z geometry of enol silyl ethers is controlled by the geometry of the starting enyne moiety. Thus, (E)- and (Z)-enol silyl ethers are obtained from (Z)- and (E)-ynenoylsilans, respectively. The 2-siloxyvinylallene products can participate in Diels-Alder reactions with reactive dienophiles such as PTAD, which can be achieved in a one-pot operation from ynenoylsilanes.

  16. Chiral Brønsted Acid Catalyzed Enantioselective Phosphonylation of Allylamine via Oxidative Dehydrogenation Coupling.

    PubMed

    Cheng, Ming-Xing; Ma, Ran-Song; Yang, Qiang; Yang, Shang-Dong

    2016-07-01

    A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Brønsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity. PMID:27331612

  17. Application of a C2-symmetric copper carbenoid in the enantioselective hydrosilylation of dialkyl and aryl-alkyl ketones.

    PubMed

    Albright, Abigail; Gawley, Robert E

    2011-12-14

    We report excellent reactivity and enantioselectivity of a C(2)-symmetric copper-bound N-heterocyclic carbene (NHC) in the hydrosilylation of a variety of structurally diverse ketones. This catalyst exhibits extraordinary enantioselctivity in the reduction of such challenging substrates as 2-butanone and 3-hexanone. Even at low catalyst loading (2.0 mol %), the reactions occur in under an hour at room temperature and often do not require purification beyond catalyst and solvent removal. The scope of this transformation was investigated in the reduction of 10 aryl-alkyl and alkyl-alkyl ketones. PMID:22074559

  18. Application of a C2-Symmetric Copper Carbenoid in the Enantioselective Hydrosilylation of Dialkyl and Aryl Alkyl Ketones

    PubMed Central

    Albright, Abigail; Gawley, Robert E.

    2011-01-01

    We report excellent reactivity and enantioselectivity of a C2-symmetric copper-bound N-heterocyclic carbene (NHC) in the hydrosilylation of a variety of structurally diverse ketones. This catalyst exhibits extraordinary enantioselctivity in the reduction of such challenging substrates as 2-butanone and 3-hexanone. Even at low catalyst loading (2.0 mol%) the reactions occur in under an hour at room temperature and often do not require purification beyond catalyst and solvent removal. The scope of this transformation was investigated in the reduction of ten aryl-alkyl and alkyl-alkyl ketones. PMID:22074559

  19. Enantioselective Approach to Quinolizidines: Total Synthesis of Cermizine D and Formal Syntheses of Senepodine G & Cermizine C

    PubMed Central

    Veerasamy, Nagarathanam; Carlson, Erik C.; Collett, Nathan D.; Saha, Mrinmoy

    2013-01-01

    The formal total syntheses of C5-epi-senepodine G and C5-epi-cermizine C have been accomplished through a novel diastereoselecetive, intramolecular amide Michael addition process. The total synthesis of cermizine D has been achieved through use of an organocatalyzed, heteroatom Michael addition to access a common intermediate. Additional key steps of this sequence include a matched, diastereoselective alkylation with an iodomethylphenyl sulfide and sulfone-aldehyde coupling/reductive desulfurization sequence to combine the major subunits. The utility of a Hartwig-style C-N coupling has been explored on functionally dense coupling partners. Diastereoselective conjugate additions to α,β-unsaturated sulfones has been investigated which provided the key sulfone intermediate in just six steps from commercially available starting materials. The formal syntheses of senepodine G and cermizine C have been accomplished through an intramolecular cyclization process of a N-Boc protected piperidine sulfone. PMID:23627426

  20. Crosslinked aggregates of Rhizopus oryzae lipase as industrial biocatalysts: preparation, optimization, characterization, and application for enantioselective resolution reactions.

    PubMed

    Kartal, Funda; Kilinc, Ali

    2012-07-01

    Lipase from Rhizopus oryzae (ROL) was immobilized as crosslinked enzyme aggregate (CLEA) via precipitation with ammonium sulfate and simultaneous crosslinking with glutaraldehyde. The optimum conditions of the immobilization process were determined. Lipase CLEAs showed a twofold increase in activity when Tween 80-pretreated lipase was used for CLEA preparation. CLEAs were shown to have several advantages compared to free lipase. CLEAs were more stable at 50°C and 60°C as well as for a wide range of pH. After incubation at 50°C, CLEA showed 74% of initial activity whereas free enzyme was totally inactivated. Reduction of Schiff bases has been performed for the first time in the CLEA preparation process significantly improving the chemically modified CLEAs' reusability, thus providing an enzyme with high potential for recycling even under aqueous reaction conditions where enzyme leakage is, in general, one of the major problems. The CLEA retained 91% activity after 10 cycles in aqueous medium. The immobilized enzyme was used for kinetic resolution reactions. Results showed that immobilization had an enhancing effect on the conversion (c) as well as on the enantiomeric ratio (E). ROL CLEA displayed five times higher enantioselectivity for the hydrolysis of (R,S)-1-phenylethyl acetate and likewise 1.5 times higher enantioselectivity for the transesterification of racemic (R-S)-1-phenylethanol with vinylacetate.

  1. Synthesis of Ferrocene Oxazoline N,O ligands and Their Application in Asymmetric Ethyl- and Phenylzinc Additions to Aldehydes.

    PubMed

    Nottingham, Chris; Benson, Robert; Müller-Bunz, Helge; Guiry, Patrick J

    2015-10-16

    The synthesis of a range of novel gem-disubstituted ferrocene-oxazoline ligands and their application in both the asymmetric ethyl- and phenylzinc additions to aldehydes is reported. These studies reveal that gem-disubstitution of i-Pr-containing ferrocene oxazoline ligands results in increased enantioselectivity compared to their unsubstituted counterparts. Utilizing zinc catalysis, these ligands provided a wide range of secondary alcohols in yields of up to 93% with ee's of up to >99%. An interesting crystal structure of a ferrocene oxide-lithium tetramer showing lithium-nitrogen coordination in the solid state is also presented.

  2. Catalytic asymmetric synthesis of thiols.

    PubMed

    Monaco, Mattia Riccardo; Prévost, Sébastien; List, Benjamin

    2014-12-10

    The synthesis of enantiopure thiols is of significant interest for industrial and academic applications. However, direct asymmetric approaches to free thiols have previously been unknown. Here we describe a novel organocascade that is catalyzed by a confined chiral phosphoric acid and furnishes O-protected β-hydroxythiols with excellent enantioselectivities. The method relies on an asymmetric thiocarboxylysis of meso-epoxides, followed by an intramolecular trans-esterification reaction. By varying the reaction conditions, the intermediate thioesters can also be obtained chemoselectively and enantioselectively.

  3. Catalytic Enantioselective Functionalization of Unactivated Terminal Alkenes.

    PubMed

    Coombs, John R; Morken, James P

    2016-02-18

    Terminal alkenes are readily available functional groups which appear in α-olefins produced by the chemical industry, and they appear in the products of many contemporary synthetic reactions. While the organic transformations that apply to alkenes are amongst the most studied reactions in all of chemical synthesis, the number of reactions that apply to nonactivated terminal alkenes in a catalytic enantioselective fashion is small in number. This Minireview highlights the cases where stereocontrol in catalytic reactions of 1-alkenes is high enough to be useful for asymmetric synthesis. PMID:26764019

  4. Catalytic Enantioselective Functionalization of Unactivated Terminal Alkenes.

    PubMed

    Coombs, John R; Morken, James P

    2016-02-18

    Terminal alkenes are readily available functional groups which appear in α-olefins produced by the chemical industry, and they appear in the products of many contemporary synthetic reactions. While the organic transformations that apply to alkenes are amongst the most studied reactions in all of chemical synthesis, the number of reactions that apply to nonactivated terminal alkenes in a catalytic enantioselective fashion is small in number. This Minireview highlights the cases where stereocontrol in catalytic reactions of 1-alkenes is high enough to be useful for asymmetric synthesis.

  5. Enantioselective aldol reactions with masked fluoroacetates

    NASA Astrophysics Data System (ADS)

    Saadi, Jakub; Wennemers, Helma

    2016-03-01

    Despite the growing importance of organofluorines as pharmaceuticals and agrochemicals, the stereoselective introduction of fluorine into many prominent classes of natural products and chemotherapeutic agents is difficult. One long-standing unsolved challenge is the enantioselective aldol reaction of fluoroacetate to enable access to fluorinated analogues of medicinally relevant acetate-derived compounds, such as polyketides and statins. Herein we present fluoromalonic acid halfthioesters as biomimetic surrogates of fluoroacetate and demonstrate their use in highly stereoselective aldol reactions that proceed under mild organocatalytic conditions. We also show that the methodology can be extended to formal aldol reactions with fluoroacetaldehyde and consecutive aldol reactions. The synthetic utility of the fluorinated aldol products is illustrated by the synthesis of a fluorinated derivative of the top-selling drug atorvastatin. The results show the prospects of the method for the enantioselective introduction of fluoroacetate to access a wide variety of highly functionalized fluorinated compounds.

  6. Second-Generation DBFOX Ligands for the Synthesis of β-Substituted α-Amino Acids via Enantioselective Radical Conjugate Additions

    PubMed Central

    Banerjee, Biplab; Capps, Steven G.; Kang, Junghoon; Robinson, Joshua W.; Castle, Steven L.

    2009-01-01

    A set of second-generation DBFOX ligands possessing extended aryl or benzyl-type groups was synthesized. The requisite amino alcohols were either commercially available (DBFOX/Bn) or constructed via Sharpless asymmetric aminohydroxylation (DBFOX/Nap, DBFOX/t-BuPh, DBFOX/Pip) or phase-transfer-catalyzed asymmetric alkylation (DBFOX/MeNap). Complexes of the ligands with Mg(NTf2)2 were evaluated as promoters of enantioselective radical conjugate additions to α,β-unsaturated α-nitro amides and esters. Reactions employing the DBFOX/Nap ligand exhibited improved enantioselectivity relative to previously published additions mediated by DBFOX/Ph. However, the relatively modest increase in diastereomeric ratio suggests that our substrate–Lewis acid binding model, which was formulated based on results from DBFOX/Ph-promoted radical conjugate additions, is in need of revision. PMID:18947256

  7. Scandium(III)-catalyzed enantioselective allylation of isatins using allylsilanes.

    PubMed

    Hanhan, Nadine V; Tang, Yng C; Tran, Ngon T; Franz, Annaliese K

    2012-05-01

    The scandium(III)-catalyzed enantioselective Hosomi-Sakurai allylation of isatins with various substituted allylic silanes is described. A catalyst loading as low as 0.05 mol % is utilized at room temperature to afford the 3-allyl-3-hydroxy-2-oxindoles in excellent yields and enantioselectivity up to 99% ee, including a demonstration of a gram-scale reaction. The effects of additives and varying silyl groups were explored to demonstrate the scope and application.

  8. Enantioselective Synthesis of Homoallylic Amines through Reactions of (Pinacolato)allylborons with Aryl-, Heteroaryl-, Alkyl- or Alkene-Substituted Aldimines Catalyzed by Chiral C1-Symmetric NHC–Cu Complexes

    PubMed Central

    Vieira, Erika M.; Snapper, Marc L.; Hoveyda, Amir H.

    2011-01-01

    A catalytic method for enantioselective synthesis of homoallylamides through Cu-catalyzed reactions of stable and easily accessible (pinacolato)allylborons with aryl-, heteroaryl-,alkyl- or alkenyl-substituted N-phosphinoylimines is disclosed. Transformations are promoted by 1–5 mol % of readily accessible NHC–Cu complexes, derived from C1-symmetric imidazolinium salts, which can be prepared in multi-gram quantities in four steps from commercially available materials. Allyl additions deliver the desired products in up to quantitative yield and 98.5:1.5 enantiomeric ratio and are amenable to gram-scale operations. A mechanistic model accounting for the observed selectivity levels and trends is proposed. PMID:21341657

  9. Stereoselective Synthesis and Modelling-Driven Optimisation of Carane-Based Aminodiols and 1,3-Oxazines as Catalysts for the Enantioselective Addition of Diethylzinc to Benzaldehyde.

    PubMed

    Szakonyi, Zsolt; Csőr, Árpád; Csámpai, Antal; Fülöp, Ferenc

    2016-05-17

    The reductive amination of (-)-2-carene-3-aldehyde, prepared in two steps from (-)-perillaldehyde, furnished 2-carene-based allylamines. tert-Butyloxycarbonyl (Boc) or carbobenzyloxy (Cbz) protection of the resulting amines, followed by stereoselective dihydroxylation in highly stereospecific reactions with OsO4 and subsequent deprotection, resulted in N-benzylaminodiols, which were transformed to primary and tertiary aminodiols. The reactions of the N-benzyl- and N-(1-phenylethyl)-substituted derivatives with formaldehyde led to highly regioselective ring closure, resulting in carane-fused 1,3-oxazines. The aminodiols and their 1,3-oxazine derivatives were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. The best (R) enantioselectivity was observed in the case of the N-((R)-1-phenylethyl)-substituted aminodiol, whereas the opposite chiral direction was preferred when the 1,3-oxazines were applied. Through the use of molecular modelling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modelling at the RHF/LANL2DZ level of theory was successfully applied for a mechanism-based interpretation of the stereochemical outcome of the reactions leading to the development of further 1,3-oxazine-based ligands, which display excellent (S) enantioselectivity (95 and 98 % ee) in the examined transformation. PMID:27072603

  10. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  11. Enantioselective Michael addition of water.

    PubMed

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-02-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry.

  12. Enantioselective Synthesis of 3,3-Disubstituted Oxindoles Bearing Two Different Heteroatoms at the C3 Position by Organocatalyzed Sulfenylation and Selenenylation of 3-Pyrrolyl-oxindoles.

    PubMed

    You, Yong; Wu, Zhi-Jun; Wang, Zhen-Hua; Xu, Xiao-Ying; Zhang, Xiao-Mei; Yuan, Wei-Cheng

    2015-08-21

    Catalytic asymmetric sulfenylation and selenenylation of 3-pyrrolyl-oxindoles for the synthesis of 3,3-disubstituted oxindoles bearing two different heteroatoms at the C3 position have been achieved with commercially available cinchonidine as catalyst. A wide range of optically active 3-thio-3-pyrrolyl-oxindoles and 3-seleno-3-pyrrolyl-oxindoles could be smoothly obtained under mild conditions with satisfactory results. The promising applicability of the protocol was also demonstrated by large-scale production.

  13. A Green Enantioselective Aldol Condensation for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Bennett, George D.

    2006-01-01

    A number of laboratory exercises for the organic chemistry curriculum that emphasize enantioselective synthesis of the aldol condensation which involves the proline-catalyzed condensation between acetone and isobutyraldehyde are explored. The experiment illustrates some of the trade-offs involved in green chemistry like the use of acetone in large…

  14. PCN pincer palladium(II) complex catalyzed enantioselective hydrophosphination of enones: synthesis of pyridine-functionalized chiral phosphine oxides as NC(sp(3))O pincer preligands.

    PubMed

    Hao, Xin-Qi; Huang, Juan-Juan; Wang, Tao; Lv, Jing; Gong, Jun-Fang; Song, Mao-Ping

    2014-10-17

    A series of chiral PCN pincer Pd(II) complexes VI-XIII with aryl-based aminophosphine-imidazoline or phosphinite-imidazoline ligands were synthesized and characterized. They were examined as enantioselective catalysts for the hydrophosphination of enones. Among them, complex IX, which features a Ph2PO donor as well as an imidazoline donor with (4S)-phenyl and N-Tol-p groups, was found to be the optimal catalyst. Thus, in the presence of 2-5 mol % of complex IX a wide variety of enones reacted smoothly with diarylphosphines to give the corresponding chiral phosphine derivatives in high yields with enantioselectivities of up to 98% ee. In particular, heteroaryl species such as 2-thienyl-, 2-furyl-, and 2-pyridinyl-containing enones that have a strong coordination ability to the Pd center were also appropriate substrates for the current catalytic system. For example, hydrophosphination of 2-alkenoylpyridines with diphenylphosphine followed by oxidation with H2O2 afforded the corresponding pyridine-functionalized chiral phosphine oxides in good yields with good to excellent enantioselectivities (10 examples, up to 95% ee). Furthermore, it had been demonstrated that the obtained pyridine-containing phosphine oxide acted as a tridentate ligand in the reaction with PdCl2 to form an intriguing NCsp(3)O pincer Pd(II) complex via Csp(3)-H bond activation, which to our knowledge is the first example of a chiral DCsp(3)D' Pd pincer (D ≠ D'; D and D' denote donor atoms such as P, N, etc.).

  15. Enantioselective synthesis of dihydrocoumarin derivatives by chiral scandium(III)-complex catalyzed inverse-electron-demand hetero-Diels-Alder reaction.

    PubMed

    Hu, Haipeng; Liu, Yangbin; Guo, Jing; Lin, Lili; Xu, Yali; Liu, Xiaohua; Feng, Xiaoming

    2015-03-01

    An asymmetric inverse-electron-demand hetero-Diels-Alder reaction between o-quinone methides and azlactones to generate potentially pharmacological active dihydrocoumarins has been achieved efficiently by using a chiral N,N'-dioxide-Sc(III) complex as the catalyst. The desired products were obtained in high yields with excellent enantioselectivities and diastereoselectivities (up to 94% yield, 96% ee and >19 : 1 dr) under mild reaction conditions. A concerted reaction pathway was confirmed by Operando IR and control experiments.

  16. Enantioselective hydroformylation of aniline derivatives.

    PubMed

    Joe, Candice L; Tan, Kian L

    2011-09-16

    We have developed a ligand that reversibly binds to aniline substrates, allowing for the control of regioselectivity and enantioselectivity in hydroformylation. In this paper we address how the electronics of the aniline ring affect both the binding of the substrate to the ligand and the enantioselectivity in this reaction.

  17. Biogenetically Inspired Synthesis of Lingzhiol.

    PubMed

    Sharmah Gautam, Krishna; Birman, Vladimir B

    2016-04-01

    A concise stereo- and enantioselective synthesis of lingzhiol has been achieved featuring a biogenetically inspired Brønsted acid catalyzed semipinacol rearrangement of a glycidyl alcohol intermediate.

  18. Catalytic Enantioselective Carboannulation with Allylsilanes

    PubMed Central

    Ball-Jones, Nicolas R.; Badillo, Joseph J.; Tran, Ngon T.; Franz, Annaliese K.

    2015-01-01

    The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a Sc(III)-indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]-borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (via trapping of the β-silyl carbocation) is also described. PMID:25045133

  19. Catalytic enantioselective carboannulation with allylsilanes.

    PubMed

    Ball-Jones, Nicolas R; Badillo, Joseph J; Tran, Ngon T; Franz, Annaliese K

    2014-09-01

    The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a scandium(III)/indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]-borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon center are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (by trapping of the β-silyl carbocation) is also described. PMID:25045133

  20. Enantioselective Hydrogenation of β,β-Disubstituted Unsaturated Carboxylic Acids under Base-Free Conditions.

    PubMed

    Yan, Qiaozhi; Kong, Duanyang; Zhao, Wei; Zi, Guofu; Hou, Guohua

    2016-03-01

    An additive-free enantioselective hydrogenation of β,β-disubstituted unsaturated carboxylic acids catalyzed by the Rh-(R,R)-f-spiroPhos complex has been developed. Under mild conditions, a wide scope of β,β-disubstituted unsaturated carboxylic acids were hydrogenated to the corresponding chiral carboxylic acids with excellent enantioselectivities (up to 99.3% ee). This methodology was also successfully applied to the synthesis of the pharmaceutical molecule indatraline.

  1. Cooperative, highly enantioselective phosphinothiourea catalysis of imine-allene [3 + 2] cycloadditions.

    PubMed

    Fang, Yuan-Qing; Jacobsen, Eric N

    2008-04-30

    A new family of phosphinthiourea catalysts was developed for the highly enantioselective synthesis of 2-aryl-2,5-hydropyrroles via a [3 + 2] cycloaddition of an electron-deficient allene with aryl and heteroaryl diphenylphosphinoylimines. The presence of both H2O and Et3N as additives was found to be important for achieving optimal rates. Dual activation of both nucleophile and electrophile by the bifunctional catalyst is invoked to account for the observed high reactivity and enantioselectivity.

  2. Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition.

    PubMed

    Xu, Hao; Golz, Christopher; Strohmann, Carsten; Antonchick, Andrey P; Waldmann, Herbert

    2016-06-27

    An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst. PMID:27193834

  3. Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups

    NASA Astrophysics Data System (ADS)

    Meng, Fanke; Li, Xiben; Torker, Sebastian; Shi, Ying; Shen, Xiao; Hoveyda, Amir H.

    2016-09-01

    structure and reaction type, by means of density functional theory calculations. The utility of the approach is highlighted by an application towards enantioselective synthesis of the anti-HIV agent (-)-equisetin.

  4. Cobalt(III) Werner Complexes with 1,2-Diphenylethylenediamine Ligands: Readily Available, Inexpensive, and Modular Chiral Hydrogen Bond Donor Catalysts for Enantioselective Organic Synthesis.

    PubMed

    Lewis, Kyle G; Ghosh, Subrata K; Bhuvanesh, Nattamai; Gladysz, John A

    2015-03-25

    In the quest for new catalysts that can deliver single enantiomer pharmaceuticals and agricultural chemicals, chemists have extensively mined the "chiral pool", with little in the way of inexpensive, readily available building blocks now remaining. It is found that Werner complexes based upon the D3 symmetric chiral trication [Co(en)3](3+) (en = 1,2-ethylenediamine), which features an earth abundant metal and cheap ligand type, and was among the first inorganic compounds resolved into enantiomers 103 years ago, catalyze a valuable carbon-carbon bond forming reaction, the Michael addition of malonate esters to nitroalkenes, in high enantioselectivities and without requiring inert atmosphere conditions. The title catalysts, [Co((S,S)-dpen)3](3+) ((S,S)-3 (3+)) 3X(-), employ a commercially available chiral ligand, (S,S)-1,2-diphenylethylenediamine. The rates and ee values are functions of the configuration of the cobalt center (Λ/Δ) and the counteranions, which must be lipophilic to solubilize the trication in nonaqueous media. The highest enantioselectivities are obtained with Λ and 2Cl(-)BArf (-), 2BF4 (-)BArf (-), or 3BF4 (-) salts (BArf (-) = B(3,5-C6H3(CF3)2)4 (-)). The substrates are not activated by metal coordination, but rather by second coordination sphere hydrogen bonding involving the ligating NH2 groups. Crystal structures and NMR data indicate enthalpically stronger interactions with the NH moieties related by the C3 symmetry axis, as opposed to those related by the C2 symmetry axes; rate trends and other observations suggest this to be the catalytically active site. Both Λ- and Δ-(S,S)-3 (3+) 2Cl(-)BArf (-) are effective catalysts for additions of β-ketoesters to RO2CN=NCO2R species (99-86% yields, 81-76% ee), which provide carbon-nitrogen bonds and valuable precursors to α-amino acids. PMID:27162946

  5. Cobalt(III) Werner Complexes with 1,2-Diphenylethylenediamine Ligands: Readily Available, Inexpensive, and Modular Chiral Hydrogen Bond Donor Catalysts for Enantioselective Organic Synthesis

    PubMed Central

    2015-01-01

    In the quest for new catalysts that can deliver single enantiomer pharmaceuticals and agricultural chemicals, chemists have extensively mined the “chiral pool”, with little in the way of inexpensive, readily available building blocks now remaining. It is found that Werner complexes based upon the D3 symmetric chiral trication [Co(en)3]3+ (en = 1,2-ethylenediamine), which features an earth abundant metal and cheap ligand type, and was among the first inorganic compounds resolved into enantiomers 103 years ago, catalyze a valuable carbon–carbon bond forming reaction, the Michael addition of malonate esters to nitroalkenes, in high enantioselectivities and without requiring inert atmosphere conditions. The title catalysts, [Co((S,S)-dpen)3]3+ ((S,S)-33+) 3X–, employ a commercially available chiral ligand, (S,S)-1,2-diphenylethylenediamine. The rates and ee values are functions of the configuration of the cobalt center (Λ/Δ) and the counteranions, which must be lipophilic to solubilize the trication in nonaqueous media. The highest enantioselectivities are obtained with Λ and 2Cl–BArf–, 2BF4–BArf–, or 3BF4– salts (BArf– = B(3,5-C6H3(CF3)2)4–). The substrates are not activated by metal coordination, but rather by second coordination sphere hydrogen bonding involving the ligating NH2 groups. Crystal structures and NMR data indicate enthalpically stronger interactions with the NH moieties related by the C3 symmetry axis, as opposed to those related by the C2 symmetry axes; rate trends and other observations suggest this to be the catalytically active site. Both Λ- and Δ-(S,S)-33+ 2Cl–BArf– are effective catalysts for additions of β-ketoesters to RO2CN=NCO2R species (99–86% yields, 81–76% ee), which provide carbon–nitrogen bonds and valuable precursors to α-amino acids. PMID:27162946

  6. Enantioselectivity in the phytotoxicity of herbicide imazethapyr.

    PubMed

    Zhou, Qingyan; Xu, Chao; Zhang, Yongsong; Liu, Weiping

    2009-02-25

    Chiral compounds usually behave enantioselectively in phyto-biochemical processes. With the increasing application of chiral herbicides, their enantioselective phytotoxicity to plants merits further study, and little information is available in this area. The purpose of this study was to examine the enantioselective phytotoxicity of the herbicide imazethapyr (IM) on the roots of maize (Zea mays L.) seedlings. Enantiomers of IM were separated by HPLC, and their absolute configurations were confirmed as S-(+)-IM and R-(-)-IM by the octant rule. Plant growth measurements and morphological, microscopic, and ultrastructural observations were conducted after treatment with individual IM enantiomers and the racemate. Observations of root morphology showed that the root diameter significantly increased, whereas the root volume, surface area, and number of root tips decreased significantly. IM enantiomers selectively damaged root hair growth and significantly reduced the sloughing of border cells from the tips. IM also had adverse effects on cell organelles, such as statocytes, mitochondria, dictyosomes, and endoplasmic reticulum in maize roots. Moreover, cell membranes and cell walls were thicker than usual after IM treatment. All of the results showed the same trend that the R-(-)-IM affected the root growth of maize seedlings more severely than the S-(+)-IM. The inhibition abilities of (+/-)-IM was between S-(+)- and R-(-)-IM. The behavior of the active enantiomer, instead of just the racemate, may have more relevance to the herbicidal effects and ecological safety of IM. Therefore, enantiomeric differences should be considered when evaluating the bioavailability of the herbicide IM.

  7. Enantioselective nitrile anion cyclization to substituted pyrrolidines. A highly efficient synthesis of (3S,4R)-N-tert-butyl-4-arylpyrrolidine-3-carboxylic acid.

    PubMed

    Chung, John Y L; Cvetovich, Raymond; Amato, Joseph; McWilliams, J Christopher; Reamer, Robert; DiMichele, Lisa

    2005-04-29

    [reaction: see text] A practical asymmetric synthesis of N-tert-butyl disubstituted pyrrolidines via a nitrile anion cyclization strategy is described. The five-step chromatography-free synthesis of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (2) from 2-chloro-1-(2,4-difluorophenyl)-ethanone achieved a 71% overall yield. The cyclization substrate was prepared via a catalytic CBS asymmetric reduction, t-butylamine displacement of the chlorohydrin, and a conjugate addition of the hindered secondary amine to acrylonitrile. The key nitrile anion 5-exo-tet cyclization concomitantly formed the pyrrolidine ring with clean inversion of the C-4 center to afford 1,3,4-trisubstituted chiral pyrrolidine in >95% yield and 94-99% ee. Diethyl chlorophosphate and lithium hexamethyldisilazide were shown to be the respective optimum activating group and base in this cyclization. The trans-cis mixture of the pyrrolidine nitrile undergoes a kinetically controlled epimerization/ saponification to afford the pure trans-pyrrolidine carboxylic acid target compound in >99.9% chemical and optical purity. This chemistry was also shown to be applicable to both electronically neutral and rich substituted phenyl substrates.

  8. Enantioselective catalytic double and triple carbonylation of olefins

    SciTech Connect

    Sperrle, M.; Consiglio, G.

    1995-12-31

    The first enantioselective double carbonylation of olefins to succinates was realized using PdX{sub 2}(L-L) complexes (X is a weakly or non-coordinating anion, L-L a chelate phosphorus ligand) as the catalyst precursor. With [Pd(H{sub 2}O){sub 2}((S)-2,2{prime}-dimethoxy-6,6{prime}-bis(diphenyl-phosphino)biphenyl)][CF{sub 3}SO{sub 3}]{sub 2} high enantioselectivity (up to 95% ee) for styrene (R = C{sub 6}H{sub 5}) was achieved. For aliphatic olefins with the same catalytic system enantioselectivity is modest (15-30% ee). Basic ligands such as 2,2{prime}-dimethoxy-6,6{prime}-bis(dicyclohexylphosphino)-biphenyl bring about an improvement of the enantioselectivity (e.g., {approximately}70% for propene). By increasing the carbon monoxide pressure an increasing formation of other products, namely dimethyl 2-oxoglutarates is observed. This is the first observed example of a triple carbonylation of olefins. Even though the chemoselectivity is not high, this reaction allows a one step synthesis of substituted 2-oxoglutarates with fair to excellent enantioselectivity (e.e. up to 95%). The reaction is completely regioselective for styrene giving exclusive formation of dimethyl 2-oxo-3-phenylglutarate (R = C{sub 6}H{sub 5}); with aliphatic olefins two regioisomers are usually formed. For propene various diphosphine ligands have been used. The enantioselectivity is interpreted on the basis of an asymmetric induction that is mostly sterically controlled and that arises from an interplay between regioselectivity and enantioface selection during olefin insertion.

  9. Enantioselective syntheses of the alkaloids cis-195A (pumiliotoxin C) and trans-195A based on multiple applications of asymmetric catalysis.

    PubMed

    Gärtner, Martin; Qu, Jianping; Helmchen, Günter

    2012-01-20

    Short enantio- and diastereoselective syntheses of the decahydroquinoline alkaloids cis- (pumiliotoxin C) and trans-195A are presented. Key steps are an enantioselective iridium-catalyzed allylic amination, a Suzuki-Miyaura coupling, a catalyst-controlled copper-catalyzed 1,4-addition, and a reductive amination. PMID:22175856

  10. A Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale

    PubMed Central

    Davis, Tyler A.; Vilgelm, Anna E.; Richmond, Ann; Johnston, Jeffrey N.

    2013-01-01

    Chiral nonracemic cis-4,5-bis(aryl) imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (−)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (−20 °C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (−)-Nutlin-3 in a 17 gram batch, and elimination of all but three chromatographic purifications. PMID:24127627

  11. Dynamic control of chirality in phosphine ligands for enantioselective catalysis

    PubMed Central

    Zhao, Depeng; Neubauer, Thomas M.; Feringa, Ben L.

    2015-01-01

    Chirality plays a fundamental role in biology and chemistry and the precise control of chirality in a catalytic conversion is a key to modern synthesis most prominently seen in the production of pharmaceuticals. In enantioselective metal-based catalysis, access to each product enantiomer is commonly achieved through ligand design with chiral bisphosphines being widely applied as privileged ligands. Switchable phosphine ligands, in which chirality is modulated through an external trigger signal, might offer attractive possibilities to change enantioselectivity in a catalytic process in a non-invasive manner avoiding renewed ligand synthesis. Here we demonstrate that a photoswitchable chiral bisphosphine based on a unidirectional light-driven molecular motor, can be used to invert the stereoselectivity of a palladium-catalysed asymmetric transformation. It is shown that light-induced changes in geometry and helicity of the switchable ligand enable excellent selectivity towards the racemic or individual enantiomers of the product in a Pd-catalysed desymmetrization reaction. PMID:25806856

  12. Enantioselective Synthesis of Axially Chiral Biaryls by the Pd-Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations

    PubMed Central

    Shen, Xiaoqiang; Jones, Gavin O.; Watson, Donald A.; Bhayana, Brijesh; Buchwald, Stephen L.

    2010-01-01

    We report efficient syntheses of axially chiral biaryl amides in yields ranging from 80–92%, and with enantioselectivity in the range 88–94% ee employing an asymmetric Suzuki-Miyaura process with Pd(OAc)2 and KenPhos as ligand. These studies demonstrate that electron-rich and electron-deficient o-halobenzamides can be efficiently coupled with 2-methyl-1-naphthylboronic acid and 2-ethoxy-1-naphthylboronic acid. The yields and selectivities of the reactions are independent of the nature of halogen substituent on the benzamide coupling partner. Our investigations demonstrate that axially chiral heterocyclic and biphenyl compounds can also be synthesized with this methodology. We also report computational studies used to determine the origin of stereoselectivity during the selectivity-determining reductive elimination step of the related coupling of tolyl boronic acid with naphthylphosphonate bromide that was reported in a previous publication (J. Am. Chem. Soc. 2000, 122, 12051–12052). These studies indicate that the stereoselectivity arises from a combination of weak -(C)H•••O interactions as well as steric interactions between the tolyl and naphthylphosphonate addends in the transition state for C-C coupling. PMID:20698695

  13. An Asymmetric Total Synthesis of Brevisamide

    PubMed Central

    Li, Jianfeng

    2009-01-01

    An enantioselective synthesis of marine alkaloid brevisamide was accomplished in a convergent manner. The synthesis utilized an enantioselective hetero-Diels-Alder reaction which sets three chiral centers in compound 11. The synthesis also features a modified Wolff-Kishner reduction, Rubottom oxidation and Suzuki-Miyaura coupling to furnish brevisamide. PMID:19694486

  14. APPLICATIONS OF CAPILLARY ELECTROPHORESIS TO THE STUDY OF CHIRAL ENVIRONMENTAL POLLUTANTS: ENANTIOMER SEPARATION AND MEASUREMENTS OF ENANTIOSELECTIVITY

    EPA Science Inventory

    CE is rarely used for routine environmental analysis of organic pollutants -- certainly not to the extent of gas chromatography or high pressure liquid chromatography. There are advantages to CE, however, that belie this lack of application. For example, CE is preferred over GC f...

  15. Enantioselective Rh-Catalyzed Hydroacylation of Olefins: From Serendipitous Discovery to Rational Design

    PubMed Central

    Murphy, Stephen K.

    2015-01-01

    Rh-catalysed hydroacylation allows the construction of chiral ketones from olefins and aldehydes. Since James' and Young's serendipitous discovery of the enantioselective 4-pentenal cyclisation, both intra and intermolecular variants have emerged that enable broader applications. PMID:25277153

  16. Enantioselective CuH-catalyzed anti-Markovnikov hydroamination of 1,1-disubstituted alkenes.

    PubMed

    Zhu, Shaolin; Buchwald, Stephen L

    2014-11-12

    Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could be employed to deliver product in undiminished yield and selectivity, demonstrating the practicality of this method for large-scale synthesis. PMID:25339089

  17. Cationic Chiral Fluorinated Oxazaborolidines. More Potent, Second-Generation Catalysts for Highly Enantioselective Cycloaddition Reactions.

    PubMed

    Mahender Reddy, Karla; Bhimireddy, Eswar; Thirupathi, Barla; Breitler, Simon; Yu, Shunming; Corey, E J

    2016-02-24

    The coordination of chiral ligands to Lewis acid metal derivatives, a useful strategy for enantioselective, electrophilic catalysis, generally leads to a lower level of catalytic activity than that of the original uncomplexed compound. Activation by further attachment of a proton or strong Lewis acid to the complex provides a way to overcome the deactivating effect of a chiral ligand. The research described herein has demonstrated that further enhancement of catalytic activity is possible by the judicious placement of fluorine substituents in the chiral ligand. This approach has led to a new, second-generation family of chiral oxazaborolidinium cationic species which can be used to effect many Diels-Alder reactions in >95% yield and >95% ee using catalyst loadings at the 1-2 mol % level. The easy recovery of the chiral ligand makes the application of these new catalysts especially attractive for large-scale synthesis.

  18. Decarboxylative Grob-type fragmentations in the synthesis of trisubstituted Z olefins: application to peloruside A, discodermolide, and epothilone D.

    PubMed

    Prantz, Kathrin; Mulzer, Johann

    2009-01-01

    Discriminating elimination: A new method for the synthesis of methyl-branched trisubstituted Z olefins, a structural motif in many polyketides with anticancer activity, relies on an (-)OH-induced decarboxylative Grob-type fragmentation (see scheme; Ms = mesyl). The starting materials are beta-mesyloxy lactones with a quaternary alpha center, which are prepared by aldol reactions in a diastereo- and enantioselective manner.

  19. Silica-Supported Cationic Gold(I) Complexes as Heterogeneous Catalysts for Regio- and Enantioselective Lactonization Reactions.

    PubMed

    Shu, Xing-Zhong; Nguyen, Son C; He, Ying; Oba, Fadekemi; Zhang, Qiao; Canlas, Christian; Somorjai, Gabor A; Alivisatos, A Paul; Toste, F Dean

    2015-06-10

    An efficient method for the synthesis of heterogeneous gold catalysts has been developed. These catalysts were easily assembled from readily available silica materials and gold complexes. The heterogeneous catalysts exhibited superior reactivity in various reactions where protodeauration is the rate-limiting step. Dramatic enhancement in regio- and enantioselectivity was observed when compared to the homogeneous unsupported gold catalyst. The catalysts are easily recovered and recycled up to 11 times without loss of enantioselectivity. PMID:26023883

  20. Enantioselective aldol reaction between isatins and cyclohexanone catalyzed by amino acid sulphonamides.

    PubMed

    Wang, Jun; Liu, Qi; Hao, Qing; Sun, Yanhua; Luo, Yiming; Yang, Hua

    2015-04-01

    Sulphonamides derived from primary α-amino acid were successfully applied to catalyze the aldol reaction between isatin and cyclohexanone under neat conditions. More interestingly, molecular sieves, as privileged additives, were found to play a vital role in achieving high enantioselectivity. Consequently, high yields (up to 99%) along with good enantioselectivities (up to 92% ee) and diastereoselectivities (up to 95:5 dr) were obtained. In addition, this reaction was also conveniently scaled up, demonstrating the applicability of this protocol.

  1. MICROWAVE TECHNOLOGY CHEMICAL SYNTHESIS APPLICATIONS

    EPA Science Inventory

    Microwave-accelerated chemical syntheses in various solvents as well as under solvent-free conditions have witnessed an explosive growth. The technique has found widespread application predominantly exploiting the inexpensive unmodified household microwave (MW) ovens although th...

  2. Applicability of the Rayleigh equation for enantioselective metabolism of chiral xenobiotics by microsomes, hepatocytes and in-vivo retention in rabbit tissues

    PubMed Central

    Jammer, Shifra; Gelman, Faina; Lev, Ovadia

    2016-01-01

    In this study we propose a new approach for analyzing the enantioselective biodegradation of some antidepressant drugs mediated by human and rat liver microsomes by using the Rayleigh equation to describe the enantiomeric enrichment−conversion dependencies. Analysis of reported degradation data of additional six pesticides, an alpha blocker and a flame retardant by microsomes or hepatocytes in vitro reaffirmed the universality of the approach. In all the in vitro studied cases that involved enantioselective degradation, a Rayleigh dependence of the enantiomeric enrichment was observed. Published data regarding in vivo retention of myclobutanil in liver, kidney, muscle and brain tissues of rabbits following injection of the racemate were remodeled showing prevalence of the Rayleigh law for the chiral enrichment of the fungicide in the various tissues. This approach will revolutionize data organization in metabolic pathway research of target xenobiotics by either liver microsomes, hepatocytes or their organ-specific in vivo retention. The fact that the enantiomeric enrichment as a function of the conversion can be described by a single quantifier, will pave the road for the use of structure activity predictors of the enantiomeric enrichment and for mechanistic discrimination based on parametric dependence of the quantifier. PMID:27021918

  3. Chiral Brønsted acid-catalyzed Friedel-Crafts alkylation of electron-rich arenes with in situ-generated ortho-quinone methides: highly enantioselective synthesis of diarylindolylmethanes and triarylmethanes.

    PubMed

    Saha, Satyajit; Alamsetti, Santosh Kumar; Schneider, Christoph

    2015-01-28

    We disclose herein a highly enantioselective protocol for the Brønsted acid-catalyzed addition of indoles and phenols to in situ-generated ortho-quinone methides which deliver broadly substituted diarylindolylmethanes and triarylmethanes, respectively, in a one-pot reaction under very mild conditions. A chiral phosphoric acid catalyst has been developed for this process serving to convert the starting ortho-hydroxybenzhydryl alcohols into the reactive ortho-quinone methides and to control the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding. PMID:25493449

  4. Radiation synthesis and fabrication for biomedical applications

    NASA Astrophysics Data System (ADS)

    Kaetsu, Isao

    1995-09-01

    Radiation synthesis and fabrication techniques can make various specific forms and structures of materials enhancedly which are useful for biomedical applications. Those materials are a porous gel and membrane, an interpenetrating networked(IPN) hydrogel, a heterogeneous surface phase membrane, an ultra-thin membrane, a biofunctional laminate and an ultra-fine particle. Radiation techniques can attach various biofunctionalities to those materials effectively by means of immobilization of biofunctional components such as enzymes, proteins, hormones, drugs, microbial cells and tissue cells. It is convenient that the immobilization can be finished at the same time as the synthesis and fabrication in many cases. The applications to bioreactors, biosensors, artificial organs, drug delivery systems and recently to signal responsive chemical delivery systems, have been studied and developed based on those techniques.

  5. Ethylene glycol: properties, synthesis, and applications.

    PubMed

    Yue, Hairong; Zhao, Yujun; Ma, Xinbin; Gong, Jinlong

    2012-06-01

    Ethylene glycol (EG) is an important organic compound and chemical intermediate used in a large number of industrial processes (e.g. energy, plastics, automobiles, and chemicals). Indeed, owing to its unique properties and versatile commercial applications, a variety of chemical systems (e.g., catalytic and non-catalytic) have been explored for the synthesis of EG, particularly via reaction processes derived from fossil fuels (e.g., petroleum, natural gas, and coal) and biomass-based resources. This critical review describes a broad spectrum of properties of EG and significant advances in the prevalent synthesis and applications of EG, with emphases on the catalytic reactivity and reaction mechanisms of the main synthetic methodologies and applied strategies. We also provide an overview regarding the challenges and opportunities for future research associated with EG. PMID:22488259

  6. Concise and enantioselective synthesis of Fmoc-Pmp(But)2-OH and design of potent Pmp-containing Grb2-SH2 domain antagonists.

    PubMed

    Li, Peng; Zhang, Manchao; Peach, Megan L; Liu, Hongpeng; Yang, Dajun; Roller, Peter P

    2003-08-21

    [reaction: see text] L-Phosphonomethylphenylalanine (L-Pmp) is an important phosphatase-resistant pTyr analogue. A most concise and stereoselective approach to the synthesis of the suitably protected Fmoc-Pmp(Bu(t))(2)-OH was developed in order to incorporate the functionally significant L-Pmp residue into peptides and peptidomimetics efficiently using standard Fmoc protocol. With this key building block, we are able to efficiently synthesize a series of potent Pmp-containing Grb2-SH2 domain antagonists, which can be used as chemotherapeutic leads for the treatment of erbB2-overexpressed breast cancer.

  7. A general enantioselective approach to jasmonoid fragrances: synthesis of (+)-(1R,2S)-methyl dihydrojasmonate and (+)-(1R,2S)-magnolione.

    PubMed

    Porta, Alessio; Vidari, Giovanni; Zanoni, Giuseppe

    2005-06-10

    Methyl dihydrojasmonate 1 and magnolione 3 are of both academic and industrial interest. In this paper, we describe a flexible, high-yielding route to diastereomerically pure (+)-cis-(1R,2S)-methyl dihydrojasmonate 1 and the first synthesis of (+)-cis-(1R,2S)-magnolione 3, both with enantiomeric excesses up to 93%. The two syntheses diverged from the same advanced intermediate 5, readily available from the enantioenriched hydroxymethyl delta-lactone (-)-(3aS,4S,6aR)-6. The olfactory properties of (1R,2S)-1 and (1R,2S)-3 are reported.

  8. Synthesis, Properties, and Applications Of Boron Nitride

    NASA Technical Reports Server (NTRS)

    Pouch, John J.; Alterovitz, Samuel A.

    1993-01-01

    Report describes synthesis, properties, and applications of boron nitride. Especially in thin-film form. Boron nitride films useful as masks in x-ray lithography; as layers for passivation of high-speed microelectronic circuits; insulating films; hard, wear-resistant, protective films for optical components; lubricants; and radiation detectors. Present status of single-crystal growth of boron nitride indicates promising candidate for use in high-temperature semiconductor electronics.

  9. Efficient enantioselective synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by Leifsonia xyli CCTCC M 2010241 using isopropanol as co-substrate.

    PubMed

    Ouyang, Qi; Wang, Pu; Huang, Jin; Cai, Jinbo; He, Junyao

    2013-03-01

    (R)-[3,5-Bis(trifluoromethyl)phenyl] ethanol is a key chiral intermediate for the synthesis of aprepitant. In this paper, an efficient synthetic process for (R)-[3,5- bis(trifluoromethyl)phenyl] ethanol was developed via the asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone, catalyzed by Leifsonia xyli CCTCC M 2010241 cells using isopropanol as the co-substrate for cofactor recycling. Firstly, the substrate and product solubility and cell membrane permeability of biocatalysts were evaluated with different co-substrate additions into the reaction system, in which isopropanol manifested as the best hydrogen donor of coupled NADH regeneration during the bioreduction of 3,5-bis(trifluoromethyl) acetophenone. Subsequently, the optimization of parameters for the bioreduction were undertaken to improve the effectiveness of the process. The determined efficient reaction system contained 200 mM of 3,5-bis(trifluoromethyl) acetophenone, 20% (v/v) of isopropanol, and 300 g/l of wet cells. The bioreduction was executed at 30°C and 200 rpm for 30 h, and 91.8% of product yield with 99.9% of enantiometric excess (e.e.) was obtained. The established bioreduction reaction system could tolerate higher substrate concentrations of 3,5- bis(trifluoromethyl) acetophenone, and afforded a satisfactory yield and excellent product e.e. for the desired (R)-chiral alcohol, thus providing an alternative to the chemical synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol.

  10. Gold(I)-catalyzed enantioselective [4 + 2]-cycloaddition of allene-dienes.

    PubMed

    González, Ana Z; Toste, F Dean

    2010-01-01

    An enantioselective gold(I)-catalyzed intramolecular [4 + 2]-cycloaddition of allenes and dienes is reported. The reactions allow for the asymmetric synthesis of trans-hexahydroindenes and pyrrolidine products using C(3)-symmetric phosphitegold(I) and ortho-arylphosphoramiditegold(I) complexes as catalysts, respectively.

  11. Gold(I)-catalyzed enantioselective [4 + 2]-cycloaddition of allene-dienes.

    PubMed

    González, Ana Z; Toste, F Dean

    2010-01-01

    An enantioselective gold(I)-catalyzed intramolecular [4 + 2]-cycloaddition of allenes and dienes is reported. The reactions allow for the asymmetric synthesis of trans-hexahydroindenes and pyrrolidine products using C(3)-symmetric phosphitegold(I) and ortho-arylphosphoramiditegold(I) complexes as catalysts, respectively. PMID:19961192

  12. Dendrimers: synthesis, applications, and properties

    PubMed Central

    2014-01-01

    Dendrimers are nano-sized, radially symmetric molecules with well-defined, homogeneous, and monodisperse structure that has a typically symmetric core, an inner shell, and an outer shell. Their three traditional macromolecular architectural classes are broadly recognized to generate rather polydisperse products of different molecular weights. A variety of dendrimers exist, and each has biological properties such as polyvalency, self-assembling, electrostatic interactions, chemical stability, low cytotoxicity, and solubility. These varied characteristics make dendrimers a good choice in the medical field, and this review covers their diverse applications. PMID:24994950

  13. Synthesis and device applications of graphitic nanomaterials

    NASA Astrophysics Data System (ADS)

    Umair, Ahmad

    This thesis is focused on two topics: (i) synthesis and characterization of bilayer graphene and pyrolytic carbon by atmospheric pressure chemical vapor deposition, and (ii) application of graphene in the fabrication of a buckyball memory device. Monolayer and bilayer graphene are semi-metal with zero bandgap. One can induce a bandgap in bilayer graphene by applying a gate voltage in the stacking direction. Thus, bandgap and Fermi level in bilayer graphene can be controlled simultaneously with a double-gate device, making it a useful material for future semiconducting applications. Controlled synthesis of bilayer graphene would be the first step to fabricate bilayer graphene based devices. In this context, we report a uniform and low-defect synthesis of bilayer graphene on evaporated nickel films. Ultra-fast cooling is employed to control the number of layers and sample uniformity. The process is self-limiting, which leads to bilayer graphene synthesis over a wide range of growth-time and precursor flow-rate. Pryolytic carbon is another important carbon nanomaterial, due to its diverse applications in electronic and biomedicalengineering. We employ chemical vapor deposition with ultra-fast cooling technique to synthesize pyrolytic carbon. Furthermore, we elucidate a method to calculate the in-plane crystal size by using Raman spectroscopy. Finally, the use of bilayer graphene in a write-once read-many memory device has been demonstrated. The device showed irreversible switching from low-resistance to high-resistance state, with hysteresis in the transport characteristics. The control sample showed random switching and hysteresis due to electromigration of metal atoms into the active material of the device. We attribute the reliability and performance of the reported device to the ultra-smooth graphene contacts, which additionally inhibits electromigration from the underlying metallic film. Moreover, the memory device showed excellent endurance and retention

  14. Germanium nanocrystals: Synthesis, characterization, and applications

    NASA Astrophysics Data System (ADS)

    Gerung, Henry

    The aim of this work was to demonstrate a simple synthesis route of Ge nanostructures (nanoparticles and nanowires), to characterize the physical and optical properties of Ge nanocrystal, and to demonstrate their biological and optoelectronics applications. The appropriate organometallic Ge 2+ precursors for the synthesis of Ge nanocrystals were identified. These precursors were used to develop a simple route that produced high quality Ge nanocrystals in high yield under mild conditions without using potentially contaminating catalysts and forming byproducts. The particle size was varied from 1 to 10 nm, depending on the reaction parameters. The relatively low-temperature, low-pressure nanocrystal synthesis condition allowed the use of organic solvents and surfactants. We also demonstrated morphological control over Ge nanocrystals via Ge2+ precursor reactivity modification. During synthesis, the surfactants passivate the nanocrystal surface and minimize surface oxidation. This synthesis method allowed optical characterization of Ge nanocrystals decoupled from contamination and oxidation. When excited with photons, Ge nanoparticles exhibit quantum confinement effect in both infrared and ultraviolet regions, as well as optical nonlinearity by the presence of two-photon absorption. These free-standing Ge nanocrystals could be further become integral elements in various optoelectronic devices. Herein, the production of water-soluble Ge nanoparticles was demonstrated as a proof of the effectiveness of our synthesis method. Addition of secondary layer surfactants such as cationic cetyltrimethylammonium bromide (CTAB) or functionalized polyethylene glycol (PEG), transforms the Ge nanoparticles to become water-soluble. The biocompatible, functionalized, water-soluble Ge nanoparticles were bound to extracellular receptors and also incorporated into the cells as a proof-of-concept demonstration for potential biomarker applications. In expectation of forming a 3-D

  15. N-Heterocyclic carbene-catalyzed [4 + 2] cyclization of α,β-unsaturated carboxylic acids bearing γ-H with isatins: an enantioselective synthesis of spirocyclic oxindole-dihydropyranones.

    PubMed

    Zhu, Ling; Yu, Chenxia; Li, Tuanjie; Wang, Yuhong; Lu, Yinan; Wang, Wenjing; Yao, Changsheng

    2016-01-28

    An NHC-catalyzed asymmetric [4 + 2] annulation of isatins and α,β-unsaturated carboxylic acids bearing γ-H gave spirocyclic oxindole-dihydropyranones successfully via an in situ activation strategy. This protocol featured easy availability of raw materials, good yields and excellent enantioselectivities (up to 99% ee).

  16. Pheromone syntheses: a tropical approach. Enantioselective synthesis of the (2R,6S,10S) and (2S,6S,10S) isomers of methyl 2,6,10-trimethyldodecanoate.

    PubMed

    Ferreira, J T; Zarbin, P H

    1996-03-01

    The enantioselective syntheses of two stereoisomers, (2R,6S,10S) and (2S,6S,10S), of methyl 2,6,10-trimethyldodecanote, out of eight possible isomers, are described , employing the stereoselective hydroboration of (-)-isopulegol (2) and (+)-neo-isopulegol (2a) as the key reaction. PMID:8733616

  17. Diastereo- and enantioselective three-component coupling approach to highly substituted pyrrolidines.

    PubMed

    Chaulagain, Mani Raj; Felten, Albert E; Gilbert, Kevin; Aron, Zachary D

    2013-09-20

    The enantioselective synthesis of substituted pyrrolidines through a mild Lewis-acid catalyzed three-component coupling reaction between picolinaldehyde, amino acids, and activated olefins is reported. The reaction uses low catalyst loadings of commercially available chiral diamines and copper triflate proposed to self-assemble in conjunction with the chelating aldehydes, 4-substituted-2-picolinaldehydes or 4-methylthiazole-2-carboxaldehyde, to generate a catalyst complex. A model is provided to explain how this complex directs enantioselectivity. This work represents a significant advance in the ease, scope, and cost of producing highly substituted, enantioenriched pyrrolidines.

  18. Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel-Crafts-Type 1,4-Addition.

    PubMed

    Yoshida, Keisuke; Itatsu, Yukihiro; Fujino, Yuta; Inoue, Hiroki; Takao, Ken-Ichi

    2016-06-01

    The highly enantioselective organocatalytic construction of spiroindanes containing an all-carbon quaternary stereocenter by intramolecular Friedel-Crafts-type 1,4-addition is described. The reaction was catalyzed by a cinchonidine-based primary amine and accelerated by water and p-bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (-)-cannabispirenones A and B. PMID:27111396

  19. Enantioselective Rh(I)-Catalyzed Addition of Arylboronic Acids to Cyclic Ketimines.

    PubMed

    Kong, Jongrock; McLaughlin, Mark; Belyk, Kevin; Mondschein, Ryan

    2015-11-20

    A method for the enantioselective synthesis of chiral α-tertiary amines via Rh-catalyzed 1,2-addition of arylboronic acids to cyclic ketimines is described. The products are efficiently accessed in good yields and excellent enantioselectivities using a commercially available chiral ligand. The reaction scope includes vinyl, aryl, and heteroarylboronic acids with yields ranging from 40% to 99% and enantiomeric excesses from 88% to 99%. Conversion of an addition product into an α,α-diaryl-substituted amino acid is also demonstrated.

  20. Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel-Crafts-Type 1,4-Addition.

    PubMed

    Yoshida, Keisuke; Itatsu, Yukihiro; Fujino, Yuta; Inoue, Hiroki; Takao, Ken-Ichi

    2016-06-01

    The highly enantioselective organocatalytic construction of spiroindanes containing an all-carbon quaternary stereocenter by intramolecular Friedel-Crafts-type 1,4-addition is described. The reaction was catalyzed by a cinchonidine-based primary amine and accelerated by water and p-bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (-)-cannabispirenones A and B.

  1. Squaramide-Catalyzed Enantioselective Michael Addition of Masked Acyl Cyanides to Substituted Enones

    PubMed Central

    2013-01-01

    Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective Michael addition to substituted enones. The reactions are catalyzed by chiral squaramides and afford adducts in high yields (90–99%) and with excellent enantioselectivities (85–98%). The addition products are unmasked to produce dicyanohydrins that, upon treatment with a variety of nucleophiles, provide γ-keto acids, esters, and amides. The use of this umpolung synthon has enabled, in enantiomerically enriched form, the first total synthesis of the prenylated phenol (+)-fornicin C. PMID:24090310

  2. Diastereo- and enantioselective three-component coupling approach to highly substituted pyrrolidines.

    PubMed

    Chaulagain, Mani Raj; Felten, Albert E; Gilbert, Kevin; Aron, Zachary D

    2013-09-20

    The enantioselective synthesis of substituted pyrrolidines through a mild Lewis-acid catalyzed three-component coupling reaction between picolinaldehyde, amino acids, and activated olefins is reported. The reaction uses low catalyst loadings of commercially available chiral diamines and copper triflate proposed to self-assemble in conjunction with the chelating aldehydes, 4-substituted-2-picolinaldehydes or 4-methylthiazole-2-carboxaldehyde, to generate a catalyst complex. A model is provided to explain how this complex directs enantioselectivity. This work represents a significant advance in the ease, scope, and cost of producing highly substituted, enantioenriched pyrrolidines. PMID:23952564

  3. Polyferrocenylsilanes: synthesis, properties, and applications.

    PubMed

    Hailes, Rebekah L N; Oliver, Alex M; Gwyther, Jessica; Whittell, George R; Manners, Ian

    2016-10-01

    This in-depth review covers progress in the area of polyferrocenylsilanes (PFS), a well-established, readily accessible class of main chain organosilicon metallopolymer consisting of alternating ferrocene and organosilane units. Soluble, high molar mass samples of these materials were first prepared in the early 1990s by ring-opening polymerisation (ROP) of silicon-bridged [1]ferrocenophanes (sila[1]ferrocenophanes). Thermal, transition metal-catalysed, and also two different living anionic ROP methodologies have been developed: the latter permit access to controlled polymer architectures, such as monodisperse PFS homopolymers and block copolymers. Depending on the substituents, PFS homopolymers can be amorphous or crystalline, and soluble in organic solvents or aqueous media. PFS materials have attracted widespread attention as high refractive index materials, electroactuated redox-active gels, fibres, films, and nanoporous membranes, as precursors to nanostructured magnetic ceramics, and as etch resists to plasmas and other radiation. PFS block copolymers form phase-separated iron-rich, redox-active and preceramic nanodomains in the solid state with applications in nanolithography, nanotemplating, and nanocatalysis. In selective solvents functional micelles with core-shell structures are formed. Block copolymers with a crystallisable PFS core-forming block were the first to be found to undergo "living crystallisation-driven self-assembly" in solution, a controlled method of assembling block copolymers into 1D or 2D structures that resembles a living covalent polymerisation, but on a longer length scale of 10 nm-10 μm. PMID:27348354

  4. Enantioselective recognition at mesoporous chiral metal surfaces

    PubMed Central

    Wattanakit, Chularat; Côme, Yémima Bon Saint; Lapeyre, Veronique; Bopp, Philippe A.; Heim, Matthias; Yadnum, Sudarat; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2014-01-01

    Chirality is widespread in natural systems, and artificial reproduction of chiral recognition is a major scientific challenge, especially owing to various potential applications ranging from catalysis to sensing and separation science. In this context, molecular imprinting is a well-known approach for generating materials with enantioselective properties, and it has been successfully employed using polymers. However, it is particularly difficult to synthesize chiral metal matrices by this method. Here we report the fabrication of a chirally imprinted mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and chiral template molecules. The porous platinum retains a chiral character after removal of the template molecules. A matrix obtained in this way exhibits a large active surface area due to its mesoporosity, and also shows a significant discrimination between two enantiomers, when they are probed using such materials as electrodes. PMID:24548992

  5. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

    NASA Astrophysics Data System (ADS)

    Behenna, Douglas C.; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E.; Virgil, Scott C.; Stoltz, Brian M.

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.

  6. Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

    PubMed Central

    2013-01-01

    Summary Enantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. PMID:24062828

  7. Black Phosphorus Nanosheets: Synthesis, Characterization and Applications.

    PubMed

    Eswaraiah, Varrla; Zeng, Qingsheng; Long, Yi; Liu, Zheng

    2016-07-01

    Black phosphorus (BP) is an emerging two-dimensional (2D) material with a natural bandgap, which has unique anisotropy and extraordinary physical properties. Due to its puckered structure, BP exhibits strong in-plane anisotropy unlike other layered materials. The bandgap tunability of BP enables a wide range of ultrafast electronics and high frequency optoelectronic applications ranging from telecommunications to thermal imaging covering the nearly entire electromagnetic spectrum, whereas no other 2D material has this functionality. Here, recent advances in the synthesis, fabrication, anisotropic physical properties, and BP-based devices including field effect transistors (FETs) and photodetectors, are discussed. Recent passivation approaches to address the degradation of BP, which is one of the main challenges to bring this material into real world applications, are also introduced. Finally, a comment is made on the recent developments in other emerging applications, future outlook and challenges ahead in BP research. PMID:27225670

  8. Conducting polymers: Synthesis and industrial applications

    SciTech Connect

    Gottesfeld, S.

    1995-05-01

    The Conducting Polymer project funded by the AIM Materials Program is developing new methods for the synthesis of electronically conducting polymers and is evaluating new industrial applications for these materials which will result in significant reductions in energy usage or industrial waste. The applications specifically addressed during FY 1994 are electrochemical capacitors and membranes for gas separation. As an active material in electrochemical capacitors, conducting polymers have the potential of storing large amounts of electrical energy in low cost materials. Such devices are needed in electronics for power failure back-up and peak power, in power supplies for filtering, and in electric vehicles for peak power and load leveling. As a gas electrically adapt the membrane for specific gas combinations. Potential energy savings in the US. for this application are estimated at 1 to 3 quads/yr.

  9. Synthesis and applications of monolithic HPLC columns

    NASA Astrophysics Data System (ADS)

    Liang, Chengdu

    Silica and carbon monolithic columns were synthesized and modified for liquid chromatography applications. Column configurations and cladding techniques were investigated in detail. Three novel approaches have been developed for the synthesis of bimodal porous rods. Out of these three methods, gel-casting was adopted for the synthesis of silica monoliths with ordered mesopores and uniform macropores; the use of colloidal templates and dual phase separation has been successfully implemented for the synthesis of carbon monoliths with well-controlled meso- and macro- porosities. The formation of mesopores in carbon materials has been further studied in the microphase separation of block copolymers. Electrochemical modification of carbon monoliths was discovered to be an efficient method for converting covalently bonded functionalities to carbon monoliths. N,N'-diethylaminobenzene has been attached to carbon surface for the separation of proteins and protein digests. The performances of carbon-based monolithic columns were studied intensely through frontal analysis and Van Deemter plot. Temperature and pressure effects were also investigated in carbon-based columns. The density of bonding on the modified carbon monoliths was characterized by thermogravimetric analysis.

  10. Synthesis, assembly and applications of semiconductor nanomembranes.

    PubMed

    Rogers, J A; Lagally, M G; Nuzzo, R G

    2011-09-01

    Research in electronic nanomaterials, historically dominated by studies of nanocrystals/fullerenes and nanowires/nanotubes, now incorporates a growing focus on sheets with nanoscale thicknesses, referred to as nanomembranes. Such materials have practical appeal because their two-dimensional geometries facilitate integration into devices, with realistic pathways to manufacturing. Recent advances in synthesis provide access to nanomembranes with extraordinary properties in a variety of configurations, some of which exploit quantum and other size-dependent effects. This progress, together with emerging methods for deterministic assembly, leads to compelling opportunities for research, from basic studies of two-dimensional physics to the development of applications of heterogeneous electronics. PMID:21886156

  11. C2-Symmetric diamines and their derivatives as promising organocatalysts for asymmetric synthesis

    NASA Astrophysics Data System (ADS)

    Zlotin, S. G.; Kochetkov, S. V.

    2015-11-01

    The review is devoted to the application of C2-symmetric diamines and their derivatives as organocatalysts for asymmetric reactions (aldol, Michael, Mannich, Diels-Alder reactions, desymmetrization, allylation, etc.). Amino acid derivatives, di- and polyamides (sulfamides), bisureas, bisthioureas, bisamidines and bisguanidines are considered. Significant attention is given to the effect of the catalyst structure on the mechanism of catalytic action. Successful applications of such catalysts in enantioselective synthesis of chiral biologically active compounds are summarized. The bibliography includes 181 references.

  12. Copper Catalyzed Enantioselective Alkylation of Pyrrole with β,γ-Unsaturated α-Ketoesters: Application to One-Pot Construction of the Seven-Membered Ring by Merging a Gold Catalysis.

    PubMed

    Hu, Yanbin; Li, Yanan; Zhang, Sheng; Li, Chong; Li, Lijun; Zha, Zhenggen; Wang, Zhiyong

    2015-08-21

    A highly enantioselective Friedel-Crafts alkylation of pyrrole to β,γ-unsaturated α-ketoesters was developed by virtue of a chiral copper complex, affording the alkylated derivatives of pyrrole with good yields and excellent enantioselectivities. Moreover, merging copper catalysis with gold catalysis realized a one-pot construction of the seven-membered ring to give annulated pyrroles with moderate to good yields and high enantiomeric excesses. PMID:26241822

  13. Synthesis, Characterization and Application of Water-soluble Gold and Silver Nanoclusters

    NASA Astrophysics Data System (ADS)

    Kumar, Santosh

    . Therefore, to obtain Au38 clusters as an enantiomer, the ligand employed should be chiral. The enantioselective synthesis of Au 38 capped with different chiral ligands has been reported and their chiroptical properties have been compared. The synthesis of a series of water-soluble Au nanoclusters has motivated us to study the effect of capping ligands and the core-size on their steady-state and time-resolved fluorescence properties, since the photoluminescence properties are particularly important for bioimaging and biomedical applications of nanoclusters. To gain fundamental insights into the origin of luminescence in nanoclusters, the effect of temperature on the fluorescence properties of these clusters has also been studied. The different sized nanoclusters ranging from a few dozen atoms to hundreds of atoms form a bridge between discrete atoms and the plasmonic nanocrystals; the latter involves essentially collective electron excitation-a phenomenon well explained by classical physics as opposed to quantum physics. The central question is: at what size does this transition from quantum behavior to classical behavior occur? To unravel this, we have successfully synthesized a series of silver nanoclusters. The precise formula assignment and their structural determination are still ongoing. We have successfully demonstrated the application of these water-soluble Au nanoclusters in photodynamic therapy for the treatment of cancer. We have successfully demonstrated that Au nanocluster system can produce singlet oxygen without the presence of any organic photosensitizers. In a collaborative project with Dr. Peteanu's group, the quenching efficiency of organic dyes by these water soluble nanoclusters is studied in different systems. Overall, this thesis outlines the successful synthesis of a family of water-soluble nanoclusters, their optical, chiroptical and fluorescence properties, as well as some applications of these nanoclusters.

  14. Enantioselective determination of triazole fungice tetraconazole by chiral high-performance liquid chromatography and its application to pharmacokinetic study in cucumber, muskmelon, and soils.

    PubMed

    Li, Jing; Dong, Fengshou; Xu, Jun; Liu, Xingang; Li, Yuanbo; Shan, Weili; Zheng, Yongquan

    2012-04-01

    A simple chiral high-performance liquid chromatography method with diode array detector was developed and validated for stereoselective determination of tetraconazole enantiomers in cucumber, muskmelon, and soils. Good separation was achieved at 20°C using cellulose tris-(4-methylbenzoate) as chiral stationary phase, a mixture of n-hexane and ethanol (90:10) as mobile phase at a flow rate of 0.8 ml/min. The assay method was linear over a range of concentrations (0.5-50 μg/ml) and the mean recoveries in all samples were more than 85% for the two enantiomers. The limits of detection for both enantiomers in plant and soil samples were 0.06 and 0.12 μg/g, respectively. Then, the proposed method was successfully applied to the study of enantioselective degradation of rac-tetraconazole in cucumber, muskmelon, and soils. The results showed that the degradation of two enantiomers of tetraconazole followed first-order kinetics and significantly stereoselective behavior was observed in cucumber, muskmelon, and Beijing soil. The preferential absorption and degradation of (-)-S-tetraconzole resulted in an enrichment of the (+)-R-tetraconazole residue in plant samples, whereas the (+)-R-tetraconazole showed a faster degradation in Beijing soil and the stereoselectivity might be caused by microorganisms. No stereoselective degradation was observed in Heilongjiang soil. PMID:22278951

  15. Synthesis and electronic applications of oxide-metal eutectic composites

    SciTech Connect

    Holder, J. D.; Cochran, J. K.; Hill, D. N.; Chapman, A. T.; Clark, G. W.

    1980-01-01

    A review is given of important developments in the synthesis of oxide-metal eutectic composites and the composite application in the continuing development of field emitters. Known metal oxide-metal binary and ternary eutectic systems are listed. The synthesis, electrical conductivity, thermodynamics, and applications are discussed. (FS)

  16. Nanocrystalline Zeolites: Synthesis, Mechanism, and Applications

    NASA Astrophysics Data System (ADS)

    Severance, Michael Andrew

    Nanocrystalline zeolite particles are becoming an important material in many technical applications (e.g. zeolite membranes). Synthetic methods that minimize the zeolite crystal diameter, while providing a narrow particle size distribution, are of primary importance in these technical applications. However, there are several limitations to currently existing synthetic routes aimed at producing nanozeolites and zeolite membrane devices. For example, zeolite growth in these contexts typically requires days to weeks at high temperature to crystallize. Despite excellent performance of zeolite membranes in several separation applications, the long synthesis times required undermine any practical application of these technologies. This work focuses on chemical manipulation of zeolite nucleation processes in sol gel systems in effort to address such limitations. The primary findings indicate that careful control of the nucleation stage of a clear zeolite synthesis (optically transparent sol gel) allow the formation of zeolite Y nanocrystals less than 50 nm in diameter with a polydispersity index less than 0.2. Furthermore, chemical perturbations made during the nucleation stage of zeolite Y hydrogel synthesis is shown to accelerate crystal growth by a factor of 3-4, depending on the specific sol gel chemistry. These findings are applied to the nanocrystal seeding and rapid hydrothermal growth of zeolite Y membranes on inexpensive polymeric supports. A novel synthetic method is developed to this end. Also, the chemical and physical properties of monodisperse nanocrystalline zeolite Y synthesized herein are explored by electrochemical impedance spectroscopy. It is found that the particle interface plays an important role in the ionic conductivity of nanocrystalline zeolites in contrast to their larger zeolite counterparts in analogy to other ceramic and metal oxide ion conductors. Finally, the possibility to produce novel organic and inorganic composite systems through

  17. Conducting polymers: Synthesis and industrial applications

    SciTech Connect

    Gottesfeld, S.

    1997-04-01

    The Conducting Polymer project funded by the AIM Program has developed new methods for the synthesis of conducting polymers and evaluated new industrial applications for these materials which will result in significant reductions in energy usage or industrial waste. The applications specifically addressed during FY 1996 included two ongoing efforts on membranes for gas separation and on electrochemical capacitors and a third new application: electrochemical reactors (ECRs) based on polymeric electrolytes. As a gas separation membrane, conducting polymers offer high selectivity and the potential to chemically or electrically adapt the membrane for specific gas combinations. Potential energy savings in the US for this application are estimated at 1 to 3 quads/yr. As an active material in electrochemical capacitors, electronically conducting polymers have the potential of storing large amounts of electric energy in low cost materials. Potential energy savings estimated at 1 quad/yr would result from introduction of electrochemical capacitors as energy storage devices in power trains of electric and hybrid vehicles, once such vehicles reach 20% of the total transportation market in the US. In the chlor-alkali industry, electrochemical reactors based on polymer electrolyte membranes consume around 1 % of the total electric power in the US. A new activity, started in FY 1996, is devoted to energy efficient ECRs. In the case of the chlor-alkali industry, energy savings as high as 50% seem possible with the novel ECR technology demonstrated by the author in 1996.

  18. A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination

    PubMed Central

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2015-01-01

    Amines with remote stereocenters (stereocenters that are three or more bonds away from the C–N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here we report a copper hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters, and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original C–C double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process. PMID:26791897

  19. Nanostructured metal foams: synthesis and applications

    SciTech Connect

    Luther, Erik P; Tappan, Bryce; Mueller, Alex; Mihaila, Bogdan; Volz, Heather; Cardenas, Andreas; Papin, Pallas; Veauthier, Jackie; Stan, Marius

    2009-01-01

    Fabrication of monolithic metallic nanoporous materials is difficult using conventional methodology. Here they report a relatively simple method of synthesizing monolithic, ultralow density, nanostructured metal foams utilizing self-propagating combustion synthesis of novel metal complexes containing high nitrogen energetic ligands. Nanostructured metal foams are formed in a post flame-front dynamic assembly with densities as low as 0.011 g/cc and surface areas as high as 270 m{sup 2}/g. They have produced metal foams via this method of titanium, iron, cobalt, nickel, zirconium, copper, palladium, silver, hafnium, platinum and gold. Microstructural features vary as a function of composition and process parameters. Applications for the metal foams are discussed including hydrogen absorption in palladium foams. A model for the sorption kinetics of hydrogen in the foams is presented.

  20. Optical nanoparticles: synthesis and biomedical application

    NASA Astrophysics Data System (ADS)

    Nhung Tran, Hong; Nghiem, Thi Ha Lien; Thuy Duong Vu, Thi; Chu, Viet Ha; Huan Le, Quang; Nhung Hoang, Thi My; Thanh Nguyen, Lai; Pham, Duc Minh; Thuan Tong, Kim; Hoa Do, Quang; Vu, Duong; Nghia Nguyen, Trong; Tan Pham, Minh; Nguyen Duong, Cao; Thuy Tran, Thanh; Son Vu, Van; Thuy Nguyen, Thi; Nguyen, Thi Bich Ngoc; Tran, Anh Duc; Thuong Trinh, Thi; Nguyen, Thi Thai An

    2015-01-01

    This paper presents a summary of our results on studies of synthesis and biomedical application of optical nanoparticles. Gold, dye-doped silica based and core-shell multifunctional multilayer (SiO2/Au, Fe3O4/SiO2, Fe3O4/SiO2/Au) water-monodispersed nanoparticles were synthesized by chemical route and surface modified with proteins and biocompatible chemical reagents. The particles were conjugated with antibody or aptamer for specific detecting and imaging bacteria and cancer cells. The photothermal effects of gold nanoshells (SiO2/Au and Fe3O4/SiO2/Au) on cells and tissues were investigated. The nano silver substrates were developed for surface enhanced Raman scattering (SERS) spectroscopy to detect melamine.

  1. Enantioselective synthesis of helicenequinones and -bisquinones.

    PubMed

    Urbano, Antonio; Carreño, M Carmen

    2013-02-01

    A convergent approach based on Diels-Alder reactions between polycyclic dienes and benzoquinones has emerged as a powerful tool for the construction of helicenequinones and bisquinones. Chemical resolution and asymmetric Diels-Alder reactions with sulfinyl quinones provide direct access to enantiopure derivatives. Biaryl or ferrocenyl dienes can be resolved leading to helicenequinones having additional axial or planar chirality.

  2. The Enantioselective Total Synthesis of Exochomine.

    PubMed

    Gao, Alison X; Hamada, Tomoaki; Snyder, Scott A

    2016-08-22

    Molecules that possess fully substituted chiral centers are often challenging to construct, particularly if those centers connect two seemingly different halves or include a nitrogen atom. Herein, we describe an efficient approach to a molecule that combines both challenges in a single center in the form of exochomine. Failures in direct coupling led to a design fueled by highly specific reaction conditions for several steps and the development of an improved protocol for 1,4-reduction in a hindered context where numerous side reactions were possible. These chemoselective solutions should have value to other problems. Challenges in obtaining matching spectral data for the synthesized natural product are also discussed. PMID:27443416

  3. Enantioselective environmental toxicology of chiral pesticides.

    PubMed

    Ye, Jing; Zhao, Meirong; Niu, Lili; Liu, Weiping

    2015-03-16

    The enantioselective environmental toxic effect of chiral pesticides is becoming more important. As the industry develops, increasing numbers of chiral insecticides and herbicides will be introduced into use, potentially posing toxic effects on nontarget living beings. Chiral pesticides, including herbicides such as acylanilides, phenoxypropanoic acids, and imidazolinones, and insecticides such as synthetic pyrethroids, organophosphates, and DDT often behave enantioselectively during agricultural use. These compounds also pose unpredictable enantioselective ecological threats to nontarget living beings and/or humans, affecting the food chain and entire ecosystems. Thus, to investigate the enantioselective toxic effects of chiral insecticides and herbicides is necessary during environmental protection. The environmental toxicology of chiral pesticides, especially the findings obtained from studies conducted in our laboratory during the past 10 years, is reviewed. PMID:25643169

  4. Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

    NASA Astrophysics Data System (ADS)

    Lichtor, Phillip A.; Miller, Scott J.

    2012-12-01

    Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis has provided the only precedents. Although non-enzymatic catalysts that meet some of these challenges became known, a comprehensive solution has remained elusive. Here, we describe low molecular weight peptide-based catalysts, discovered through a combinatorial synthesis and screening protocol, that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features reminiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for the asymmetric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternative-site selectivity in comparison to oxidation catalysts previously described.

  5. Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

    PubMed Central

    Lichtor, Phillip A.; Miller, Scott J.

    2012-01-01

    Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis provided the only precedents. Although nonenzymatic catalysts are now known that meet some of these challenges, a comprehensive solution has remained elusive. Here, we describe low molecular weight, peptide-based catalysts discovered through a combinatorial synthesis and screening protocol that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features remiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for asymmertric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternate site-selectivity in comparison to previously described oxidation catalysts. PMID:23174978

  6. Chiral hypervalent iodine reagents: synthesis and reactivity.

    PubMed

    Parra, Alejandro; Reboredo, Silvia

    2013-12-16

    Chiral hypervalent iodine chemistry has been steadily increasing in importance in recent years. This review catalogues enantioselective transformations triggered by chiral hypervalent iodine(III/V) reagents, in stoichiometric or catalytic quantities, highlighting the different reactivities in terms of yield and enantioselectivity. Moreover, the synthesis of the most remarkable and successful catalysts has been illustrated in detail.

  7. Hyperbranched polyphosphates: synthesis, functionalization and biomedical applications.

    PubMed

    Liu, Jinyao; Huang, Wei; Pang, Yan; Yan, Deyue

    2015-06-21

    Hyperbranched polyphosphates (HBPPs) are newly emerged polymeric biomaterials with repeating phosphate bonds in a highly branched framework over the past 5 years. Due to the integration of the advantages of both hyperbranched polymers and polyphosphates, HBPPs are versatile in chemical structure, flexible in physicochemical properties, water soluble, biocompatible and biodegradable in biological features. On the basis of their excellent water solubility, biocompatibility, biodegradability and potential functionalization as well as their simple preparation in one-pot synthesis, HBPPs have fascinating biomedical applications, especially for drug delivery. In this tutorial review, the recent advances of HBPPs are summarized. HBPPs with different topological structures and various functionalities were synthesized via adjusting the side group of cyclic phosphate monomers, which have shown promising biomedical applications, for example, using as a macromolecular anticancer agent and constructing advanced drug delivery systems, including site-specific delivery systems, self-delivery systems, and stimuli-responsive delivery systems. Such progress may promote the further development of interdisciplinary research between polymer chemistry, material science and biomedicine.

  8. Enantioselective α-alkenylation of aldehydes with boronic acids via the synergistic combination of copper(II) and amine catalysis.

    PubMed

    Stevens, Jason M; MacMillan, David W C

    2013-08-14

    The enantioselective α-alkenylation of aldehydes has been accomplished using boronic acids via the synergistic combination of copper and chiral amine catalysis. The merger of two highly utilized and robust catalytic systems has allowed for the development of a mild and operationally trivial protocol for the direct formation of α-formyl olefins employing common building blocks for organic synthesis. PMID:23889497

  9. Synthesis of γ-Valerolactone from Carbohydrates and its Applications.

    PubMed

    Zhang, Zehui

    2016-01-01

    γ-Valerolactone (GVL) is a valuable chemical intermediate that can be obtained by catalytic reduction of levulinic acid (LA) or alkyl levulinates (AL). There are many reports on the synthesis of GVL from LA or AL. However, the demand for the large-scale synthesis of GVL requires more environmentally friendly and cost-effective production processes. This article focuses on the recent advance in the synthesis of GVL from carbohydrates or lignocellulosic biomass. In addition, application of GVL as the reaction solvents, fuel additives, and as precursor for the synthesis of jet fuel and polymer monomers is also discussed.

  10. Synthesis and applications of heterostructured semiconductor nanocrystals

    NASA Astrophysics Data System (ADS)

    Khon, Elena

    Semiconductor nanocrystals (NCs) have been of great interest to researchers for several decades due to their unique optoelectronic properties. These nanoparticles are widely used for a variety of different applications. However, there are many unresolved issues that lower the efficiency and/or stability of devices which incorporate these NCs. Our research is dedicated to addressing these issues by identifying potential problems and resolving them, improving existing systems, generating new synthetic strategies, and/or building new devices. The general strategies for the synthesis of different nanocrystals were established in this work, one of which is the colloidal growth of gold domains onto CdS semiconductor nanocrystals. Control of shape and size was achieved simply by adjusting the temperature and the time of the reaction. Depending on the exact morphology of Au and CdS domains, fabricated nano-composites can undergo evaporation-induced self-assembly onto a substrate, which is very useful for building devices. CdS/Au heterostructures can assemble in two different ways: through end-to-end coupling of Au domains, resulting in the formation of one-dimensional chains; and via side-by-side packing of CdS nanorods, leading to the onset of two-dimensional superlattices. We investigated the nature of exciton-plasmon interactions in Au-tipped CdS nanorods using femtosecond transient absorption spectroscopy. The study demonstrated that the key optoelectronic properties of electrically coupled metal and semiconductor domains are significantly different from those observed in systems with weak inter-domain coupling. In particular, strongly-coupled nanocomposites promote mixing of electronic states at semiconductor-metal domain interfaces, which causes a significant suppression of both plasmon and exciton carrier excitations. Colloidal QDs are starting to replace organic molecules in many different applications, such as organic light emmiting diods (OLEDs), due to their

  11. Synthesis, characterization and applications of graphene architectures

    NASA Astrophysics Data System (ADS)

    Thomas, Abhay Varghese

    Graphene, a two--dimensional sheet of sp2 hybridized carbon atoms arranged in a honeycomb lattice structure, has garnered tremendous interest from the scientific community for its unique combination of properties. It has interesting electrical, thermal, optical and mechanical properties that scientists and engineers are trying to understand and harness to improve current products as well as focus on disruptive technologies that can be made possible by this next generation material. In this thesis the synthesis, characterization and applications of various graphene architectures were explored from the context of a bottom--up and top--down synthesis approach. The work is divided into three main chapters and each one deals with a unique architecture of graphene as well as its properties and an application to a real world problem. In Chapter 2, we focus on bottom--up synthesis of graphene sheets by chemical vapor deposition. We then studied the wetting properties of graphene coated surfaces. More specifically the wetting properties of single and multilayer graphene films on flat and nanoscale rough surfaces are explored and the insights gained are used in improving heat transfer performance of copper surfaces. Single layer graphene, on certain flat surfaces, was shown to exhibit `wetting transparency' as a result of its sheer thinness and this property is of interest in various wetting related applications. Surface protection from corrosion and/or oxidation without change in wetting properties is tremendously useful in multiple fields and we looked to apply this property to dehumidification of copper surfaces. The short time scales results demonstrated that graphene indeed served to prevent oxidation of the surface which in turn promoted increased heat transfer co--efficients with respect to the oxidized copper surfaces. Closer inspection of the surface over long time scales however revealed that the oxide layer changed the wetting properties and this was detrimental

  12. Enantioselective acyl transfer catalysis by a combination of common catalytic motifs and electrostatic interactions

    PubMed Central

    Mandai, Hiroki; Fujii, Kazuki; Yasuhara, Hiroshi; Abe, Kenko; Mitsudo, Koichi; Korenaga, Toshinobu; Suga, Seiji

    2016-01-01

    Catalysts that can promote acyl transfer processes are important to enantioselective synthesis and their development has received significant attention in recent years. Despite noteworthy advances, discovery of small-molecule catalysts that are robust, efficient, recyclable and promote reactions with high enantioselectivity can be easily and cost-effectively prepared in significant quantities (that is, >10 g) has remained elusive. Here, we demonstrate that by attaching a binaphthyl moiety, appropriately modified to establish H-bonding interactions within the key intermediates in the catalytic cycle, and a 4-aminopyridyl unit, exceptionally efficient organic molecules can be prepared that facilitate enantioselective acyl transfer reactions. As little as 0.5 mol% of a member of the new catalyst class is sufficient to generate acyl-substituted all-carbon quaternary stereogenic centres in quantitative yield and in up to 98:2 enantiomeric ratio (er) in 5 h. Kinetic resolution or desymmetrization of 1,2-diol can be performed with high efficiency and enantioselectivity as well. PMID:27079273

  13. Enantioselective functionalization of allylic C-H bonds following a strategy of functionalization and diversification.

    PubMed

    Sharma, Ankit; Hartwig, John F

    2013-11-27

    We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S, or C-C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated.

  14. Enantioselective addition of boronates to o-quinone methides catalyzed by chiral biphenols.

    PubMed

    Luan, Yi; Schaus, Scott E

    2012-12-12

    Chiral biphenols were found to catalyze the enantioselective asymmetric addition of aryl- or alkenylboronates to o-quinone methides. Substituted 2-styryl phenols were obtained in good yields (up to 95%) with high enantiomeric ratios (up to 98:2) in the presence of 10 mol % 3,3'-Br(2)-BINOL. A two-step synthesis of (S)-4-methoxydalbergione in good yield and selectivity was achieved. PMID:23206197

  15. Enantioselective Addition of Boronates to Ortho-Quinone Methides Catalyzed by Chiral Biphenols

    PubMed Central

    Luan, Yi; Schaus, Scott E.

    2014-01-01

    Chiral biphenols were found to catalyze the enantioselective asymmetric addition of aryl- or alkenyl-boronates to ortho-quinone methides. Substituted 2-styryl phenols were obtained in good yields (up to 95%) and high enantiomeric ratios (up to 98:2) in presence of 10 mol % of 3,3′-Br2-BINOL. A two step synthesis of (S)-4-Methoxy-dalbergione is achieved in good yield and selectivity. PMID:23206197

  16. A Cu/Pd Cooperative Catalysis for Enantioselective Allylboration of Alkenes.

    PubMed

    Jia, Tao; Cao, Peng; Wang, Bing; Lou, Yazhou; Yin, Xuemei; Wang, Min; Liao, Jian

    2015-11-01

    A cooperative Cu/Pd-catalyzed asymmetric three-component reaction of styrenes, B2(pin)2, and allyl carbonates was reported. This reaction, in the presence of chiral CuOAc/SOP and achiral Pd(dppf)Cl2 catalysts, occurs smoothly with high enantioselectivities (up to 97% ee) . The allylboration products, which contain alkene (or diene) unite and alkylboron group, are easily functionalized. The utility of this protocol was demonstrated through the synthesis of an antipsychotic drug, (-)-preclamol. PMID:26458555

  17. Organocatalytic enantioselective tandem aldol-cyclization reaction of α-isothiocyanato imides and activated carbonyl compounds

    PubMed Central

    Guang, Jie; Zhao, Cong-Gui

    2011-01-01

    The organocatalytic enantioselective tandem aldol-cyclization reactions of α-isothiocyanato imides and activated carbonyl compounds, such as isatins, an α-ketolactone and a 1,2-dione, have been studied with cinchona alkaloid-derived thiourea-catalysts. This methodology provided an easy way to access enantiomerically enriched spirobicyclic thiocarbamates with high yields and good to excellent stereoselectivity, which have been demonstrated to be useful precursors for the synthesis of biologically active molecules. PMID:21921975

  18. Enantioselective Alkynylation of 2-Trifluoroacetyl Imidazoles Catalyzed by Bis-Cyclometalated Rhodium(III) Complexes Containing Pinene-Derived Ligands.

    PubMed

    Zheng, Yu; Harms, Klaus; Zhang, Lilu; Meggers, Eric

    2016-08-16

    Chiral rhodium(III) complexes containing two cyclometalating 2-phenyl-5,6-(S,S)-pinenopyridine ligands and two additional acetonitriles are introduced as excellent catalysts for the highly enantioselective alkynylation of 2-trifluoroacetyl imidazoles. Whereas the ligand-based chirality permits the straightforward synthesis of the complexes in a diastereomerically and enantiomerically pure fashion, the metal-centered chirality is responsible for the asymmetric induction over the course of the catalysis. For comparison, the analogous iridium congeners provide only low enantioselectivity, and previously reported benzoxazole- and benzothiazole-based catalysts do not show any catalytic activity for this reaction under standard reaction conditions. PMID:27312941

  19. Highly Enantioselective Aza-Michael Reaction between Alkyl Amines and β-Trifluoromethyl β-Aryl Nitroolefins.

    PubMed

    Wang, Leming; Chen, Jiean; Huang, Yong

    2015-12-14

    The aza-Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza-Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N-heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza-Michael reaction between primary alkyl amines and β-trifluoromethyl β-aryl nitroolefins. In contrast to classical conjugate-addition reactions, a strategy of HOMO-raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).

  20. Enantioselective Hydrosilylation of Imines Catalyzed by Chiral Zinc Acetate Complexes.

    PubMed

    Bezłada, Agata; Szewczyk, Marcin; Mlynarski, Jacek

    2016-01-01

    A series of zinc acetate complexes with optically pure diphenylethanediamine (DPEDA)-derived ligands have been employed as enantioselective catalyst for the hydrosilylation of various imines. High control of stereoselectivity (up to 97% ee) and excellent yields (up to 96%) were gained for a broad range of N-phosphinoylimines by using (R,R)-N,N'-dibenzyl-1,2-diphenylethane-1,2-diamine. This is the first successful application of an air-stable and environmentally friendly chiral Zn(OAc)2 complex instead of the previously used harmful diethylzinc in the asymmetric reduction of the C═N double bond. PMID:26667387

  1. Chiral Sulfinamide/Achiral Sulfonic Acid Co-Catalyzed Enantioselective Protonation of Enol Silanes

    PubMed Central

    Beck, Elizabeth M.; Hyde, Alan M.

    2011-01-01

    The application of chiral sulfinamides and achiral sulfonic acids as a co-catalyst system for enantioselective protonation reactions is described. Structurally simple, easily accessible sulfinamides were found to induce moderate-to-high ee's in the formation of 2-aryl-substituted cycloalkanones from the corresponding trimethylsilyl enol ethers. PMID:21786775

  2. Copper-catalyzed enantioselective C-H functionalization of indoles with an axially chiral bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Yan, Zhong; Zhou, Yong-Gui

    2016-09-21

    Using copper complexes with an axially chiral bipyridine ligand C4-ACBP as the catalyst, an enantioselective functionalization of indoles with diazo compounds was developed with up to 95% ee. This protocol paves the way for further applications of these ligands. PMID:27529404

  3. Mechanochemical synthesis of advanced nanomaterials for catalytic applications.

    PubMed

    Xu, Chunping; De, Sudipta; Balu, Alina M; Ojeda, Manuel; Luque, Rafael

    2015-04-21

    Mechanochemical synthesis emerged as the most advantageous, environmentally sound alternative to traditional routes for nanomaterials preparation with outstanding properties for advanced applications. Featuring simplicity, high reproducibility, mild/short reaction conditions and often solvent-free condition (dry milling), mechanochemistry can offer remarkable possibilities in the development of advanced catalytically active materials. The proposed contribution has been aimed to provide a brief account of remarkable recent findings and advances in the mechanochemical synthesis of solid phase advanced catalysts as opposed to conventional systems. The role of mechanical energy in the synthesis of solid catalysts and their application is critically discussed as well as the influence of the synthesis procedure on the physicochemical properties and the efficiency of synthesized catalysts is studied. The main purpose of this feature article is to highlight the possibilities of mechanochemical protocols in (nano)materials engineering for catalytic applications.

  4. Supramolecular dendritic polymers: from synthesis to applications.

    PubMed

    Dong, Ruijiao; Zhou, Yongfeng; Zhu, Xinyuan

    2014-07-15

    CONSPECTUS: Supramolecular dendritic polymers (SDPs), which perfectly combine the advantages of dendritic polymers with those of supramolecular polymers, are a novel class of non-covalently bonded, highly branched macromolecules with three-dimensional globular topology. Because of their dynamic/reversible nature, unique topological structure, and exceptional physical/chemical properties (e.g., low viscosity, high solubility, and a large number of functional terminal groups), SDPs have attracted increasing attention in recent years in both academic and industrial fields. In particular, the reversibility of non-covalent interactions endows SDPs with the ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, such as pH, temperature, light, stress, and redox agents, which further provides a flexible and robust platform for designing and developing smart supramolecular polymeric materials and functional supramolecular devices. The existing SDPs can be systematically classified into the following six major types according to their topological features: supramolecular dendrimers, supramolecular dendronized polymers, supramolecular hyperbranched polymers, supramolecular linear-dendritic block copolymers, supramolecular dendritic-dendritic block copolymers, and supramolecular dendritic multiarm copolymers. These different types of SDPs possess distinct morphologies, unique architectures, and specific functions. Benefiting from their versatile topological structures as well as stimuli-responsive properties, SDPs have displayed not only unique characteristics or advantages in supramolecular self-assembly behaviors (e.g., controllable morphologies, specific performance, and facile functionalization) but also great potential to be promising candidates in various fields. In this Account, we summarize the recent progress in the synthesis, functionalization, and self-assembly of SDPs as well as their potential

  5. Synthesis of natural fragrant molecules cis-3-methyl-4-decanolide and aerangis lactone. General enantioselective routes to beta,gamma-cis-disubstituted gamma-lactones and gamma,delta-cis-disubstituted delta-lactones.

    PubMed

    Wu, Yikang; Shen, Xin; Tang, Chao-Jun; Chen, Zhi-Long; Hu, Qi; Shi, Wei

    2002-05-31

    General enantioselective routes to 3,4-cis-dialkyl substituted gamma-lactones and 4,5-cis-dialkyl substituted delta-lactones using TiCl(4)-mediated Evans asymmetric aldolization as the key step are reported. The syntheses are exemplified with two natural fragrant molecules, cis-3-methyl-4-decanolide (1) and aerangis lactone (2). The (R,R) steroegenic centers were established using (S)-phenylalanine-derived 2-oxazolidinone or thiazolidinethione as chiral auxiliary, whereas the (S,S) ones were constructed with auxiliary prepared from (R)-phenylglycine. NaBH(4)/CaCl(2)/THF in the presence of a small amount of EtOH was introduced as a new effective method for reductive cleavage of chiral oxazolidinone auxiliaries. Previously unknown, tricky concentration effects were observed during the monotosylation of diol 7 and BOM protection of Evans aldol 23.

  6. Asymmetric allylation of α-ketoester-derived N-benzoylhydrazones promoted by chiral sulfoxides/N-oxides Lewis bases: highly enantioselective synthesis of quaternary α-substituted α-allyl-α-amino acids.

    PubMed

    Reyes-Rangel, Gloria; Bandala, Yamir; García-Flores, Fred; Juaristi, Eusebio

    2013-09-01

    Chiral sulfoxides/N-oxides (R)-1 and (R,R)-2 are effective chiral promoters in the enantioselective allylation of α-keto ester N-benzoylhydrazone derivatives 3a-g to generate the corresponding N-benzoylhydrazine derivatives 4a-g, with enantiomeric excesses as high as 98%. Representative hydrazine derivatives 4a-b were subsequently treated with SmI2, and the resulting amino esters 5a-b with LiOH to obtain quaternary α-substituted α-allyl α-amino acids 6a-b, whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data.

  7. Applications of computer graphics to aircraft synthesis

    NASA Technical Reports Server (NTRS)

    Carmichael, R. L.; Putnam, R.

    1975-01-01

    The history of the development of an aircraft configuration synthesis program using interactive computer graphics was described. A system based on time-sharing was compared to two different concepts based on distributed computing.

  8. Enantioselective olefin metathesis with cyclometalated ruthenium complexes.

    PubMed

    Hartung, John; Dornan, Peter K; Grubbs, Robert H

    2014-09-17

    The success of enantioselective olefin metathesis relies on the design of enantioenriched alkylidene complexes capable of transferring stereochemical information from the catalyst structure to the reactants. Cyclometalation of the NHC ligand has proven to be a successful strategy to incorporate stereogenic atoms into the catalyst structure. Enantioenriched complexes incorporating this design element catalyze highly Z- and enantioselective asymmetric ring opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the difference in ring strain between these two substrates leads to different propagating species in the catalytic cycle. Asymmetric ring closing metathesis (ARCM) of a challenging class of prochiral trienes has also been achieved. The extent of reversibility and effect of reaction setup was also explored. Finally, promising levels of enantioselectivity in an unprecedented Z-selective asymmetric cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated. PMID:25137310

  9. Enantioselective olefin metathesis with cyclometalated ruthenium complexes.

    PubMed

    Hartung, John; Dornan, Peter K; Grubbs, Robert H

    2014-09-17

    The success of enantioselective olefin metathesis relies on the design of enantioenriched alkylidene complexes capable of transferring stereochemical information from the catalyst structure to the reactants. Cyclometalation of the NHC ligand has proven to be a successful strategy to incorporate stereogenic atoms into the catalyst structure. Enantioenriched complexes incorporating this design element catalyze highly Z- and enantioselective asymmetric ring opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the difference in ring strain between these two substrates leads to different propagating species in the catalytic cycle. Asymmetric ring closing metathesis (ARCM) of a challenging class of prochiral trienes has also been achieved. The extent of reversibility and effect of reaction setup was also explored. Finally, promising levels of enantioselectivity in an unprecedented Z-selective asymmetric cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated.

  10. Enantioselective Olefin Metathesis with Cyclometalated Ruthenium Complexes

    PubMed Central

    2015-01-01

    The success of enantioselective olefin metathesis relies on the design of enantioenriched alkylidene complexes capable of transferring stereochemical information from the catalyst structure to the reactants. Cyclometalation of the NHC ligand has proven to be a successful strategy to incorporate stereogenic atoms into the catalyst structure. Enantioenriched complexes incorporating this design element catalyze highly Z- and enantioselective asymmetric ring opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the difference in ring strain between these two substrates leads to different propagating species in the catalytic cycle. Asymmetric ring closing metathesis (ARCM) of a challenging class of prochiral trienes has also been achieved. The extent of reversibility and effect of reaction setup was also explored. Finally, promising levels of enantioselectivity in an unprecedented Z-selective asymmetric cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated. PMID:25137310

  11. Widely applicable synthesis of enantiomerically pure tertiary alkyl-containing 1-alkanols by zirconium-catalyzed asymmetric carboalumination of alkenes and palladium- or copper-catalyzed cross-coupling.

    PubMed

    Xu, Shiqing; Lee, Ching-Tien; Wang, Guangwei; Negishi, Ei-ichi

    2013-08-01

    A highly enantioselective and widely applicable method for the synthesis of various chiral 2-alkyl-1-alkanols, especially those of feeble chirality, has been developed. It consists of zirconium-catalyzed asymmetric carboalumination of alkenes (ZACA), lipase-catalyzed acetylation, and palladium- or copper-catalyzed cross-coupling. By virtue of the high selectivity factor (E) associated with iodine, either (S)- or (R)-enantiomer of 3-iodo-2-alkyl-1-alkanols (1), prepared by ZACA reaction of allyl alcohol, can be readily purified to the level of ≥99% ee by lipase-catalyzed acetylation. A variety of chiral tertiary alkyl-containing alcohols, including those that have been otherwise difficult to prepare, can now be synthesized in high enantiomeric purity by Pd- or Cu-catalyzed cross-coupling of (S)-1 or (R)-2 for introduction of various primary, secondary, and tertiary carbon groups with retention of all carbon skeletal features. These chiral tertiary alkyl-containing alcohols can be further converted into the corresponding acids with full retention of the stereochemistry. The synthetic utility of this method has been demonstrated in the highly enantioselective (≥99% ee) and efficient syntheses of (R)-2-methyl-1-butanol and (R)- and (S)-arundic acids.

  12. Spiro[2.4]hepta-4,6-dienes: synthesis and application in organic synthesis

    NASA Astrophysics Data System (ADS)

    Menchikov, L. G.; Nefedov, O. M.

    2016-03-01

    This review integrates and describes systematically the data in the field of spiro[2.4]hepta-4,6-dienes published in the past 15 years. The changes in the development of studies that took place during this period are noted. The methods for the synthesis, the reactivity details and key chemical transformations of spiro[2.4]hepta-4,6-dienes are considered, with the emphasis on applications of these compounds in organic synthesis. The bibliography includes 207 references.

  13. General Stereodivergent Enantioselective Total Synthetic Approach toward Macrosphelides A-G and M.

    PubMed

    Häcker, Christine; Plietker, Bernd

    2015-08-21

    A straightforward enantioselective total synthesis algorithm for the preparation of 8 out of 13 macrosphelides within 9-11 steps starting from tert-butyl sorbate is presented. The use of a cyclic sulfate as both protecting and reactivity directing group is the key element within this algorithm. A high-pressure transesterification allows for the selective ring-enlargement of the 15-membered macrosphelides into the 16-membered counterparts. The absolute configurations of the natural products were unambiguously assigned both by the chemical synthesis and by X-ray structure analysis.

  14. Enantioselective Desymmetrization of Prochiral Cyclohexanones by Organocatalytic Intramolecular Michael Additions to α,β-Unsaturated Esters**

    PubMed Central

    Gammack Yamagata, Adam D; Datta, Swarup; Jackson, Kelvin E; Stegbauer, Linus; Paton, Robert S; Dixon, Darren J

    2015-01-01

    A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83–99 % ee) and in good yields (60–90 %). Calculations revealed that stepwise C–C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst. PMID:25727215

  15. Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular Michael additions to α,β-unsaturated esters.

    PubMed

    Gammack Yamagata, Adam D; Datta, Swarup; Jackson, Kelvin E; Stegbauer, Linus; Paton, Robert S; Dixon, Darren J

    2015-04-13

    A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst. PMID:25727215

  16. Catalytic enantioselective OFF ↔ ON activation processes initiated by hydrogen transfer: concepts and challenges.

    PubMed

    Quintard, Adrien; Rodriguez, Jean

    2016-08-18

    Hydrogen transfer initiated processes are eco-compatible transformations allowing the reversible OFF ↔ ON activation of otherwise unreactive substrates. The minimization of stoichiometric waste as well as the unique activation modes provided by these transformations make them key players for a greener future for organic synthesis. Long limited to catalytic reactions that form racemic products, considerable progress on the development of strategies for controlling diastereo- and enantioselectivity has been made in the last decade. The aim of this review is to present the different strategies that enable enantioselective transformations of this type and to highlight how they can be used to construct key synthetic building blocks in fewer operations with less waste generation. PMID:27381644

  17. Iridium-Catalyzed Enantioselective Allylic Substitution of Enol Silanes from Vinylogous Esters and Amides.

    PubMed

    Chen, Ming; Hartwig, John F

    2015-11-01

    The enol silanes of vinylogous esters and amides are classic dienes for Diels-Alder reactions. Here, we report their reactivity as nucleophiles in Ir-catalyzed, enantioselective allylic substitution reactions. A variety of allylic carbonates react with these nucleophiles to give allylated products in good yields with high enantioselectivities and excellent branched-to-linear ratios. These reactions occur with KF or alkoxide as the additive, but mechanistic studies suggest that these additives do not activate the enol silanes. Instead, they serve as bases to promote the cyclometalation to generate the active Ir catalyst. The carbonate anion, which was generated from the oxidative addition of the allylic carbonate, likely activates the enol silanes to trigger their activity as nucleophiles for reactions with the allyliridium electrophile. The synthetic utility of this method was illustrated by the synthesis of the anti-muscarinic drug, fesoterodine. PMID:26441002

  18. Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement

    PubMed Central

    2016-01-01

    Sigmatropic rearrangements number among the most powerful complexity-building transformations in organic synthesis but have remained largely insensitive to enantioselective catalysis due to the diffuse nature of their transition structures. Here, we describe a synergistic ion-binding strategy for asymmetric catalysis of anionic sigmatropic rearrangements. This approach is demonstrated with the enantioselective [2,3]-Wittig rearrangement of α-allyloxy carbonyl compounds to afford highly enantioenriched homoallylic alcohol products. Chiral thiourea catalysts are shown to engage reactive anions and their countercations through a cooperative set of attractive, noncovalent interactions. Catalyst structure–reactivity–selectivity relationship studies and computational analyses provide insight into catalyst–substrate interactions responsible for enantioinduction and allude to the potential generality of this catalytic strategy. PMID:27413786

  19. Cellulose Nanocrystals as Chiral Inducers: Enantioselective Catalysis and Transmission Electron Microscopy 3D Characterization.

    PubMed

    Kaushik, Madhu; Basu, Kaustuv; Benoit, Charles; Cirtiu, Ciprian M; Vali, Hojatollah; Moores, Audrey

    2015-05-20

    Cellulose nanocrystals (CNCs), derived from cellulose, provide us with an opportunity to devise more sustainable solutions to current technological challenges. Enantioselective catalysis, especially heterogeneous, is the preferred method for the synthesis of pure chiral molecules in the fine chemical industries. Cellulose has been long sought as a chiral inducer in enantioselective catalysis. We report herein an unprecedentedly high enantiomeric excess (ee) for Pd patches deposited onto CNCs used as catalysts for the hydrogenation of prochiral ketones in water at room temperature and 4 bar H2. Our system, where CNCs acted as support and sole chiral source, achieved an ee of 65% with 100% conversions. Cryo-electron microscopy, high-resolution transmission electron microscopy, and tomography were used for the first time to study the 3D structure of a metal functionalized CNC hybrid. It established the presence of sub-nanometer-thick Pd patches at the surface of CNCs and provided insight into the chiral induction mechanism.

  20. Iridium-catalyzed enantioselective polyene cyclization.

    PubMed

    Schafroth, Michael A; Sarlah, David; Krautwald, Simon; Carreira, Erick M

    2012-12-19

    A highly enantioselective polycyclization method has been developed using the combination of Lewis acid activation with iridium-catalyzed allylic substitution. This strategy relies on direct use of branched, racemic allylic alcohols and furnishes a diverse and unique set of carbo- and heteropolycyclic ring systems in good yields and ≥99% ee. PMID:23193947

  1. Gold(I)-catalyzed enantioselective cycloaddition reactions.

    PubMed

    López, Fernando; Mascareñas, José L

    2013-10-30

    In recent years there have been extraordinary developments of gold(I)-catalyzed enantioselective processes. This includes progress in the area of cycloaddition reactions, which are of particular interest due to their potential for the rapid construction of optically active cyclic products. In this article we will summarize some of the most remarkable examples, emphasizing reaction mechanisms and key intermediates involved in the processes.

  2. Iridium-catalyzed enantioselective polyene cyclization.

    PubMed

    Schafroth, Michael A; Sarlah, David; Krautwald, Simon; Carreira, Erick M

    2012-12-19

    A highly enantioselective polycyclization method has been developed using the combination of Lewis acid activation with iridium-catalyzed allylic substitution. This strategy relies on direct use of branched, racemic allylic alcohols and furnishes a diverse and unique set of carbo- and heteropolycyclic ring systems in good yields and ≥99% ee.

  3. A new protocol for the in situ generation of aromatic, heteroaromatic, and unsaturated diazo compounds and its application in catalytic and asymmetric epoxidation of carbonyl compounds. Extensive studies to map out scope and limitations, and rationalization of diastereo- and enantioselectivities.

    PubMed

    Aggarwal, Varinder K; Alonso, Emma; Bae, Imhyuck; Hynd, George; Lydon, Kevin M; Palmer, Matthew J; Patel, Mamta; Porcelloni, Marina; Richardson, Jeffery; Stenson, Rachel A; Studley, John R; Vasse, Jean-Luc; Winn, Caroline L

    2003-09-10

    A variety of metalated tosylhydrazone salts derived from benzaldehyde have been prepared and were reacted with benzaldehyde in the presence of tetrahydrothiophene (THT) (20 mol %) and Rh(2)(OAc)(4) (1 mol %) to give stilbene oxide. Of the lithium, sodium, and potassium salts tested, the sodium salt was found to give the highest yield and selectivity. This study was extended to a wide variety of aromatic, heteroaromatic, aliphatic, alpha,beta-unsaturated, and acetylenic aldehydes and to ketones. On the whole, high yields of epoxides with moderate to very high diastereoselectivities were observed. A broad range of tosylhydrazone salts derived from aromatic, heteroaromatic, and alpha,beta-unsaturated aldehydes was also examined using the same protocol in reactions with benzaldehyde, and again, good yields and high diastereoselectivities were observed in most cases. Thus, a general process for the in situ generation of diazo compounds from tosylhydrazone sodium salts has been established and applied in sulfur-ylide mediated epoxidation reactions. The chiral, camphor-derived, [2.2.1] bicyclic sulfide 7 was employed (at 5-20 mol % loading) to render the above processes asymmetric with a range of carbonyl compounds and tosylhydrazone sodium salts. Benzaldehyde tosylhydrazone sodium salt gave enantioselectivities of 91 +/- 3% ee and high levels of diastereoselectivity with a range of aldehydes. However, tosylhydrazone salts derived from a range of carbonyl compounds gave more variable selectivities. Although those salts derived from electron-rich or neutral aldehydes gave high enantioselectivities, those derived from electron-deficient or hindered aromatic aldehydes gave somewhat reduced enantioselectivities. Using alpha,beta-unsaturated hydrazones, chiral sulfide 7 gave epoxides with high diastereoselectivities, but only moderate yields were achieved (12-56%) with varying degrees of enantioselectivity. A study of solvent effects showed that, while the impact on

  4. Application of variable metric methods to structural synthesis

    NASA Technical Reports Server (NTRS)

    Vanderplaats, G. N.; Sugimoto, H.

    1985-01-01

    Powell (1977, 1978), Biggs (1972, 1975), and Han (1976, 1977) have developed a class of variable metric methods which create an explicit, quadratic, subproblem which is to be solved for finding a search direction for design improvement. A one-dimensional search is then performed. The present paper has the objective to present this variable metric approach in the context of structural synthesis. The variable metric algorithm is modified for application to the structural synthesis problem. The application of the new procedure is illustrated with the aid of examples, taking into account a 10-bar planar truss, a 17-bar planar tower, and a cantilever beam.

  5. Microfluidic Synthesis of Nanoparticles and their Biosensing Applications.

    PubMed

    Boken, Jyoti; Soni, Sarvesh K; Kumar, Dinesh

    2016-11-01

    We present an extensive overview of the evolution and progress made in the field of microstructures and nanostructures preparation using microfluidic techniques in recent times. A microfluidic system creates particles that are within a narrow range of shape and size distribution. It enables controlling the shape, size and composition of nanomaterials (NMs) for various applications. A brief evaluation of the advantages of both droplet-based and continuous flow synthesis of nanoparticles (NPs) is discussed in detail and compared with the traditional wet chemical batch synthesis approach. Due to increasing applications of biosensing, nanobiotechnology, nanomedicine and diagnostics devices, special attention should be paid to metal NPs developed through microfluidic routes.

  6. New pathways for organic synthesis. Practical applications of transition metals

    SciTech Connect

    Colquhoun, H.M.; Holton, J.; Thompson, D.J.; Twigg, M.V.

    1984-01-01

    This book contains a considerable number of transition-metal-based procedures that have genuine applications in synthesis, and which are arranged according to the nature of the organic product or synthetic transformation being carried out. The objective is to provide those engaged in the preparation of pharmaceuticals, natural products, herbicides, dyestuffs, and other organic chemicals with a practical guide to the application of transition metals in organic synthesis. Topics considered include the formation of carbon-carbon bonds, the formation of carbocyclic compounds, the formation of heterocyclic compounds, the isomerization of alkenes, the direct introduction and removal of carbonyl groups, reduction, oxidation, and preparing and handling transition metal catalysts.

  7. Design and synthesis of mixed oxides nanoparticles for biofuel applications

    SciTech Connect

    Chen, Senniang

    2010-05-15

    The work in this dissertation presents the synthesis of two mixed metal oxides for biofuel applications and NMR characterization of silica materials. In the chapter 2, high catalytic efficiency of calcium silicate is synthesized for transesterfication of soybean oil to biodisels. Chapter 3 describes the synthesis of a new Rh based catalyst on mesoporous manganese oxides. The new catalyst is found to have higher activity and selectivity towards ethanol. Chapter 4 demonstrates the applications of solid-state Si NMR in the silica materials.

  8. Zinc oxide nanoparticles for revolutionizing agriculture: synthesis and applications.

    PubMed

    Sabir, Sidra; Arshad, Muhammad; Chaudhari, Sunbal Khalil

    2014-01-01

    Nanotechnology is the most innovative field of 21st century. Extensive research is going on for commercializing nanoproducts throughout the world. Due to their unique properties, nanoparticles have gained considerable importance compared to bulk counterparts. Among other metal nanoparticles, zinc oxide nanoparticles are very much important due to their utilization in gas sensors, biosensors, cosmetics, drug-delivery systems, and so forth. Zinc oxide nanoparticles (ZnO NPs) also have remarkable optical, physical, and antimicrobial properties and therefore have great potential to enhance agriculture. As far as method of formation is concerned, ZnO NPs can be synthesized by several chemical methods such as precipitation method, vapor transport method, and hydrothermal process. The biogenic synthesis of ZnO NPs by using different plant extracts is also common nowadays. This green synthesis is quite safe and ecofriendly compared to chemical synthesis. This paper elaborates the synthesis, properties, and applications of zinc oxide nanoparticles. PMID:25436235

  9. Zinc Oxide Nanoparticles for Revolutionizing Agriculture: Synthesis and Applications

    PubMed Central

    Sabir, Sidra; Arshad, Muhammad

    2014-01-01

    Nanotechnology is the most innovative field of 21st century. Extensive research is going on for commercializing nanoproducts throughout the world. Due to their unique properties, nanoparticles have gained considerable importance compared to bulk counterparts. Among other metal nanoparticles, zinc oxide nanoparticles are very much important due to their utilization in gas sensors, biosensors, cosmetics, drug-delivery systems, and so forth. Zinc oxide nanoparticles (ZnO NPs) also have remarkable optical, physical, and antimicrobial properties and therefore have great potential to enhance agriculture. As far as method of formation is concerned, ZnO NPs can be synthesized by several chemical methods such as precipitation method, vapor transport method, and hydrothermal process. The biogenic synthesis of ZnO NPs by using different plant extracts is also common nowadays. This green synthesis is quite safe and ecofriendly compared to chemical synthesis. This paper elaborates the synthesis, properties, and applications of zinc oxide nanoparticles. PMID:25436235

  10. Zinc oxide nanoparticles for revolutionizing agriculture: synthesis and applications.

    PubMed

    Sabir, Sidra; Arshad, Muhammad; Chaudhari, Sunbal Khalil

    2014-01-01

    Nanotechnology is the most innovative field of 21st century. Extensive research is going on for commercializing nanoproducts throughout the world. Due to their unique properties, nanoparticles have gained considerable importance compared to bulk counterparts. Among other metal nanoparticles, zinc oxide nanoparticles are very much important due to their utilization in gas sensors, biosensors, cosmetics, drug-delivery systems, and so forth. Zinc oxide nanoparticles (ZnO NPs) also have remarkable optical, physical, and antimicrobial properties and therefore have great potential to enhance agriculture. As far as method of formation is concerned, ZnO NPs can be synthesized by several chemical methods such as precipitation method, vapor transport method, and hydrothermal process. The biogenic synthesis of ZnO NPs by using different plant extracts is also common nowadays. This green synthesis is quite safe and ecofriendly compared to chemical synthesis. This paper elaborates the synthesis, properties, and applications of zinc oxide nanoparticles.

  11. Enantioselective transesterification of glycidol catalysed by a novel lipase expressed from Bacillus subtilis.

    PubMed

    Wang, Lei; Tai, Jian-Dong; Wang, Ren; Xun, Er-Na; Wei, Xiao-Fei; Wang, Lei; Wang, Zhi

    2010-05-01

    A novel plasmid (pBSR2) was constructed by incorporating a strong lipase promoter and a terminator into the original pBD64. The lipase gene from Bacillus subtilis strain IFFI10210 was cloned into the plasmid pBSR2 and transformed into B. subtilis A.S.1.1655 to obtain an overexpression strain. The recombinant lipase [BSL2 (B. subtilis lipase 2)] has been expressed from the novel constructed strain and used in kinetic resolution of glycidol through enantioselective transesterification. The effects of reaction conditions on the activity as well as enantioselectivity were investigated. BSL2 showed a satisfying enantioselectivity (E>30) under the optimum conditions [acyl donor: vinyl butyrate; the mole ratio of vinyl butyrate to glycidol was 3:1; organic medium: 1,2-dichloroethane with water activity (a(w))=0.33; temperature 40 degrees C]. The remaining (R)-glycidol with a high enantiomeric purity [ee (enantiomeric excess) >99%] could be obtained when the conversion was approx. 60%. The results clearly show a good potential for industrial application of BSL2 in the resolution of glycidol through enantioselective transesterification.

  12. Synthesis of silver nanoparticle and its application.

    PubMed

    Pandian, A Muthu Kumara; Karthikeyan, C; Rajasimman, M; Dinesh, M G

    2015-11-01

    In this work, silver nanoparticles have been synthesized by wet chemical technique, green synthesis and microbial methods. Silver nitrate (10(-3)M) was used with aqueous extract to produce silver nanoparticles. From the results it was observed that the yield of nanoparticles was high in green synthesis. The size of the silver nanoparticles was determined from Scanning Electron Microscope analysis (SEM). Fourier Transform Infrared spectroscopy (FTIR) was carried out to determine the presence of biomolecules in them. Its cytotoxic effect was studied in cancerous cell line and normal cell line. MTT assay was done to test its optimal concentration and efficacy which gives valuable information for the use of silver nanoparticles for future cancer therapy. PMID:25866204

  13. Synthesis of silver nanoparticle and its application.

    PubMed

    Pandian, A Muthu Kumara; Karthikeyan, C; Rajasimman, M; Dinesh, M G

    2015-11-01

    In this work, silver nanoparticles have been synthesized by wet chemical technique, green synthesis and microbial methods. Silver nitrate (10(-3)M) was used with aqueous extract to produce silver nanoparticles. From the results it was observed that the yield of nanoparticles was high in green synthesis. The size of the silver nanoparticles was determined from Scanning Electron Microscope analysis (SEM). Fourier Transform Infrared spectroscopy (FTIR) was carried out to determine the presence of biomolecules in them. Its cytotoxic effect was studied in cancerous cell line and normal cell line. MTT assay was done to test its optimal concentration and efficacy which gives valuable information for the use of silver nanoparticles for future cancer therapy.

  14. Bio-Inspired Green Nanoparticles: Synthesis, Mechanism, and Antibacterial Application

    PubMed Central

    Velusamy, Palaniyandi; Kumar, Govindarajan Venkat; Jeyanthi, Venkadapathi; Das, Jayabrata; Pachaiappan, Raman

    2016-01-01

    In the recent years, noble nanoparticles have attracted and emerged in the field of biology, medicine and electronics due to their incredible applications. There were several methods have been used for synthesis of nanoparticles such as toxic chemicals and high energy physical procedures. To overcome these, biological method has been used for the synthesis of various metal nanoparticles. Among the nanoparticles, silver nanoparticles (AgNPs) have received much attention in various fields, such as antimicrobial activity, therapeutics, bio-molecular detection, silver nanocoated medical devices and optical receptor. Moreover, the biological approach, in particular the usage of natural organisms has offered a reliable, simple, nontoxic and environmental friendly method. Hence, the current article is focused on the biological synthesis of silver nanoparticles and their application in the biomedical field. PMID:27123159

  15. Synthesis and photovoltaic application of coper (I) sulfide nanocrystals

    SciTech Connect

    Wu, Yue; Wadia, Cyrus; Ma, Wanli; Sadtler, Bryce; Alivisatos, A.Paul

    2008-06-24

    We present the rational synthesis of colloidal copper(I) sulfide nanocrystals and demonstrate their application as an active light absorbing component in combination with CdS nanorods to make a solution-processed solar cell with 1.6percent power conversion efficiency on both conventional glass substrates and flexible plastic substrates with stability over a 4 month testing period.

  16. Semiconductor nanowhiskers: Synthesis, properties, and applications

    SciTech Connect

    Dubrovskii, V. G. Cirlin, G. E. Ustinov, V. M.

    2009-12-15

    Recent results of studying the semiconductor's whisker nanocrystals are reviewed. Physical grounds of growing whisker nanocrystals using the mechanism vapor-liquid-crystal are given and the main epitaxial technologies of synthesis of whisker nanocrystals are described. Thermodynamic and kinetic factors controlling the morphological properties, composition, and crystal structure of whisker nanocrystals are considered in detail. The main theoretical models of the growth and structure of whisker nanocrystals are described. The data on physical properties of whisker nanocrystals and possibilities of their use in nanophotonics, nanoelectronics, and nanobiotechnology are presented.

  17. Enantioselective Analysis in instruments onboard ROSETTA/PHILAE and ExoMars

    NASA Astrophysics Data System (ADS)

    Hendrik Bredehöft, Jan; Thiemann, Wolfram; Meierhenrich, Uwe; Goesmann, Fred

    It has been suggested a number of times in the past, to look for chirality as a biomarker. So far, for lack of appropriate instrumentation, space missions have never included enantioselective analysis. The distinction between enantiomers is of crucial importance to the question of the origin of the very first (pre)biotic molecules. If molecules detected in situ on another celestial body were found to exhibit a chiral bias, this would mean that at least partial asymmetric synthesis could take place abiotically. If this chiral bias should be found to be near 100For the currently flying ESA mission ROSETTA an enantioselective instrument was built, to try for the first time to detect and separate chiral molecules in situ. This instrument is COSAC, the Cometary Sampling and Acquisition Experiment, an enantioselective GCMS device[1,2], which is included in the lander PHLIAE that will eventually in 2014 land on the nucleus of comet 67P/Churyumov-Gerasimenko. A similar but even more powerful type of enantioselective GC-MS is in preparation for ESA's ExoMars mission. This instrument is part of MOMA, the Mars Organic Molecules Analyser. It has the objective of identifying and quantifying chiral organic molecules in surface and subsurface samples of Mars. Currently ExoMars is scheduled for 2018. The newly developed enantioselective technique utilized by both COSAC and MOMA will be described, including sample acquisition, derivatization, and separation in space-resistant chiral stationary capillary columns with time-of-flight mass spectrometric detection. Results of enantioselective analyses of representative test samples with special emphasis on amino acids[3], the building blocks of protein polymers, will be presented and we will discuss potential results of space missions Rosetta and ExoMars. [1] Thiemann W.H.-P., Meierhenrich U.: ESA Mission ROSETTA Will Probe for Chirality of Cometary Amino Acids. Origins of Life and Evolution of Biospheres 31 (2001), 199-210. [2

  18. Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methylimidazolium lactate to aquatic algae.

    PubMed

    Chen, Hui; Zou, Yuqin; Zhang, Lijuan; Wen, Yuezhong; Liu, Weiping

    2014-09-01

    With the wide application of chiral ionic liquids (CILs) as green solvents, their threats to the aquatic environment cannot be ignored. Thus, risk assessment and the prospective design of inherently safe CILs have become more urgent. However, whether enantioselectivity is a feature of the aquatic toxicity of CILs is poorly understood. Herein, we describe the first investigation into the ecotoxicities of CILs toward green algae Scenedesmus obliquus and Euglena gracilis. A series of methylimidazolium lactic ionic liquids, which cation parts with different alkyl chains and anion part is enantiomers of lactate, are used as representative CILs. The results of S. obliquus showed that the EC50 value of L-(+)-1-ethyl-3-methylimidazolium lactate (L-(+)-EMIM L) was more than 5000 μM, while the EC50 value of D-(-)-1-ethyl-3-methylimidazolium lactate (D-(-)-EMIM L) was 2255.21 μM. Such a distinct difference indicates the enantioselective toxicity of CILs to algae. This enantioselectivity initially persisted with increasing carbon chain length, but no longer exhibited when with greater carbon chain lengths, due to changes in the toxicity weightings of the cation parts. Further research showed that the enantioselective effects of CILs resulted from the differences in the production of reactive oxygen species, the damage to cell membrane integrity and cell wall after exposure to CILs. Results from this study showed that monitoring for the racemate CILs will give an inadequate or misleading environmental risk assessment. Thus, we should improve our ability to predict their effects in natural environments. In the meantime, non-selective use of CILs will do harm to aquatic organisms. Therefore, to minimize their potential for environmental impact, the enantioselective toxicities of CILs with short alkyl chains should be taken into consideration.

  19. Aqueous based reflux method for green synthesis of nanostructures: Application in CZTS synthesis.

    PubMed

    Aditha, Sai Kiran; Kurdekar, Aditya Dileep; Chunduri, L A Avinash; Patnaik, Sandeep; Kamisetti, Venkataramaniah

    2016-01-01

    The aqueous based reflux method useful for the green synthesis of nanostructures is described in detail. In this method, the parameters: the order of addition of precursors, the time of the reflux and the cooling rate should be optimized in order to obtain the desired phase and morphology of the nanostructures. The application of this method is discussed with reference to the synthesis of CZTS nanoparticles which have great potential as an absorber material in the photovoltaic devices. The highlights of this method are:•Simple.•Low cost.•Aqueous based.

  20. Aqueous based reflux method for green synthesis of nanostructures: Application in CZTS synthesis.

    PubMed

    Aditha, Sai Kiran; Kurdekar, Aditya Dileep; Chunduri, L A Avinash; Patnaik, Sandeep; Kamisetti, Venkataramaniah

    2016-01-01

    The aqueous based reflux method useful for the green synthesis of nanostructures is described in detail. In this method, the parameters: the order of addition of precursors, the time of the reflux and the cooling rate should be optimized in order to obtain the desired phase and morphology of the nanostructures. The application of this method is discussed with reference to the synthesis of CZTS nanoparticles which have great potential as an absorber material in the photovoltaic devices. The highlights of this method are:•Simple.•Low cost.•Aqueous based. PMID:27408826

  1. Aerosol synthesis and application of folded graphene-based materials

    NASA Astrophysics Data System (ADS)

    Chen, Yantao; Wang, Zhongying; Qiu, Yang

    2015-12-01

    Graphene oxide colloid has been widely used in the synthesis of various graphene-based materials. Graphene oxide sheets, with a low bending rigidity, can be folded when assembled in aqueous phase. A simple but industrial scalable way, aerosol processing, can be used to fabricate folded graphene-based materials. These folded materials can carry various cargo materials and be used in different applications such as time-controlled drug release, medical imaging enhancement, catalyst support and energy related areas. The aerosol synthesis of folded graphene-based materials can also be easily extended to fabricate hybrid nanomaterials without any complicated chemistries.

  2. Synthesis and Characterization of Polymers for Fuel Cells Application

    NASA Technical Reports Server (NTRS)

    Tytko, Stephen F.

    2003-01-01

    The goal of this summer research is to prepare Polymer Exchange Membranes (PEM s) for fuel cell application. Several high temperature polymers such as polybenzimidazoles and polyether ketones were known to possess good high temperature stability and had been investigated by post-sulfonation to yield sulfonated polymers. The research project will involve two approaches: 1. Synthesis of polybenzimidazoles and then react with alkyl sultonse to attach an aliphatic sulfonic groups. 2. Synthesis of monomers containing sulfonic acid units either on a aromatic ring or on an aliphatic chain and then polymerize the monomers to form high molecular weight sulfonate polymers.

  3. Application of olefin metathesis in the synthesis of steroids.

    PubMed

    Morzycki, Jacek W

    2011-01-01

    Over the past decade, ruthenium-mediated metathesis transformations, including cross-metathesis, ring-closing metathesis, enyne metathesis, ring-opening metathesis polymerization, and also tandem processes, belong to the most intensively studied reactions. Many applications of olefin metathesis in the synthesis of natural products have been recently described. Also in the field of steroid chemistry new methods of total synthesis and hemisynthesis based on metathesis reactions have been elaborated. Various biologically active compounds, e.g. vitamin D and hormone analogues, steroid dimers and macrocycles, etc. have been prepared using a variety of olefin-metathesis protocols.

  4. [Enantioselective determinination of R-warfarin/S-warfarin in human plasma using liquid chromatography-tandem mass spectrometry and its application in a drug-drug interaction study].

    PubMed

    Jin, Shu; Zhang, Yi-Fan; Chen, Xiao-Yan; Liu, Ke; Zhong, Da-Fang

    2012-01-01

    To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin. PMID:22493814

  5. The Construction of All-Carbon Quaternary Stereocenters by Use of Pd-Catalyzed Asymmetric Allylic Alkylation Reactions in Total Synthesis

    PubMed Central

    Hong, Allen Y.

    2014-01-01

    All-carbon quaternary stereocenters have posed significant challenges in the synthesis of complex natural products. These important structural motifs have inspired the development of broadly applicable palladium-catalyzed asymmetric allylic alkylation reactions of unstabilized non-biased enolates for the synthesis of enantioenriched α-quaternary products. This microreview outlines key considerations in the application of palladium-catalyzed asymmetric allylic alkylation reactions and presents recent total syntheses of complex natural products that have employed these powerful transformations for the direct, catalytic, enantioselective construction of all-carbon quaternary stereocenters. PMID:24944521

  6. Me2(CH2Cl)SiCN: Bifunctional Cyanating Reagent for the Synthesis of Tertiary Alcohols with a Chloromethyl Ketone Moiety via Ketone Cyanosilylation.

    PubMed

    Zeng, Xing-Ping; Zhou, Jian

    2016-07-20

    We report a novel bifunctional cyanating reagent, Me2(CH2Cl)SiCN, which paves the way to a one-pot sequential synthesis of tertiary alcohols featuring a chloromethyl ketone moiety via enantioselective ketone cyanosilylation. This method contributes to gram-scale enantioselective total synthesis of the aggregation pheromone of the Colorado potato beetle, (S)-CPB. PMID:27399262

  7. Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

    NASA Astrophysics Data System (ADS)

    Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

    Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

  8. Enantioselective Total Syntheses of Plectosphaeroic Acids B and C

    PubMed Central

    Jabri, Salman Y.

    2013-01-01

    Evolution of the synthetic strategy that culminated in the first total syntheses of the structurally unique plectosphaeroic acids B (2) and C (3) is described. The successful enantioselective route to (+)-2 and (+)-3 proceeds in 6 and 11 steps from the known hexahydro-2H-pyrazinopyrrolo[2,3-b]indole-1,4-dione 39, which in turn are available in enantiomerically pure form by chemical synthesis. The central challenge in this synthesis endeavor was uniting the hexahydro-2H-pyrazinopyrrolo[2,3-b]indole-1,4-dione and cinnabarinic acid fragments of these marine alkaloids. Critical for achieving this successful C–N bond formation was the use of an iodocinnabarinic acid diester in which the amino group was masked with two Boc substituents, a Cu(I) carboxylate complex, and the weak base KOAc. The highly congested C–N bond generated in this coupling, in conjunction with the delicate nature of the densely functionalized coupling partners, provide striking testament to the power of modern copper-mediated amination methods. Two approaches, one stereoselective, for introducing the methylthio substituents of (+)-plectosphaeroic acid B were developed. The epitrisulfide ring of (+)-plectosphaeroic acid C was formed by ring expansion of an epidisulfide precursor. PMID:24007470

  9. Biologically Relevant Glycopeptides: Synthesis and Applications

    NASA Astrophysics Data System (ADS)

    Bennett, Clay S.; Payne, Richard J.; Koeller, Kathryn M.; Wong, Chi-Huey

    Over the past two decades interest in glycopeptides and glycoproteins has intensified, due in part to the development of new and efficient methods for the synthesis of these compounds. This includes a number of chemical and enzymatic techniques for incorporating glycosylation onto the peptide backbone as well as the introduction of powerful peptide ligation methods for the construction of glycoproteins. This review discusses these methods with a special emphasis on biologically relevant glycopeptides and glycoproteins. This includes the development of a number of antigens which hold promise as potential vaccines for HIV, cancer, or a host of other clinically important diseases. In addition the development of new antibiotics aimed at overcoming the problem of resistance will be discussed. Finally, chemical and enzymatic methods for the construction of glycopeptide mimetics will be described.

  10. Application of optimality criteria in structural synthesis

    NASA Technical Reports Server (NTRS)

    Terai, K.

    1974-01-01

    The rational use of optimality criteria was investigated for a class of structural synthesis problems where materials, configuration and applied load conditions are specified, and the minimum weight design is to be determined. The potential of hybrid methods of structural optimization for dealing with relatively large design problems involving practical complexity was explored. The reduced basis concept in design space was used to decrease the number of generalized design variables dealt with by the mathematical programming algorithm. Optimality criteria methods for obtaining design vectors associated with displacement, system buckling and natural frequency constraints are presented. A stress ratio method was used to generate a basis design vector representing the stress constraints. The finite element displacement method was used as the basic structural analysis tool. Results for several examples of truss systems subject to stress, displacement and minimum size constraints are presented. An assessment of these results indicates the effectiveness of the hybrid method developed.

  11. Nanosilver particles in medical applications: synthesis, performance, and toxicity.

    PubMed

    Ge, Liangpeng; Li, Qingtao; Wang, Meng; Ouyang, Jun; Li, Xiaojian; Xing, Malcolm M Q

    2014-01-01

    Nanosilver particles (NSPs), are among the most attractive nanomaterials, and have been widely used in a range of biomedical applications, including diagnosis, treatment, drug delivery, medical device coating, and for personal health care. With the increasing application of NSPs in medical contexts, it is becoming necessary for a better understanding of the mechanisms of NSPs' biological interactions and their potential toxicity. In this review, we first introduce the synthesis routes of NSPs, including physical, chemical, and biological or green synthesis. Then the unique physiochemical properties of NSPs, such as antibacterial, antifungal, antiviral, and anti-inflammatory activity, are discussed in detail. Further, some recent applications of NSPs in prevention, diagnosis, and treatment in medical fields are described. Finally, potential toxicology considerations of NSPs, both in vitro and in vivo, are also addressed.

  12. Nanosilver particles in medical applications: synthesis, performance, and toxicity

    PubMed Central

    Ge, Liangpeng; Li, Qingtao; Wang, Meng; Ouyang, Jun; Li, Xiaojian; Xing, Malcolm MQ

    2014-01-01

    Nanosilver particles (NSPs), are among the most attractive nanomaterials, and have been widely used in a range of biomedical applications, including diagnosis, treatment, drug delivery, medical device coating, and for personal health care. With the increasing application of NSPs in medical contexts, it is becoming necessary for a better understanding of the mechanisms of NSPs’ biological interactions and their potential toxicity. In this review, we first introduce the synthesis routes of NSPs, including physical, chemical, and biological or green synthesis. Then the unique physiochemical properties of NSPs, such as antibacterial, antifungal, antiviral, and anti-inflammatory activity, are discussed in detail. Further, some recent applications of NSPs in prevention, diagnosis, and treatment in medical fields are described. Finally, potential toxicology considerations of NSPs, both in vitro and in vivo, are also addressed. PMID:24876773

  13. Nanoparticles: synthesis and applications in life science and environmental technology

    NASA Astrophysics Data System (ADS)

    Luong Nguyen, Hoang; Nguyen, Hoang Nam; Hai Nguyen, Hoang; Quynh Luu, Manh; Hieu Nguyen, Minh

    2015-03-01

    This work focuses on the synthesis, functionalization, and application of gold and silver nanoparticles, magnetic nanoparticles Fe3O4, combination of 4-ATP-coated silver nanoparticles and Fe3O4 nanoparticles. The synthesis methods such as chemical reduction, seeding, coprecipitation,and inverse microemulsion will be outlined. Silica- and amino-coated nanoparticles are suitable for several applications in biomedicine and the environment. The applications of the prepared nanoparticles for early detection of breast cancer cells, basal cell carcinoma, antibacterial test, arsenic removal from water, Herpes DNA separation, CD4+ cell separation and isolation of DNA of Hepatitis virus type B (HBV) and Epstein-Barr virus (EBV) are discussed. Finally, some promising perspectives will be pointed out. Invited talk at the 7th International Workshop on Advanced Materials Science and Nanotechnology IWAMSN2014, 2-6 November, 2014, Ha Long, Vietnam.

  14. Enantioselective Syntheses of Both Enantiomers of Noranabasamine

    PubMed Central

    Miao, Lei; DiMaggio, Stassi C.; Shu, Hong

    2009-01-01

    Both the R and S enantiomers of the amphibian alkaloid noranabasamine were prepared in > 30% overall yield with 80% ee and 86% ee, respectively. An enantioselective iridium catalyzed N-heterocyclization reaction with either (R)- or (S)-1-phenylethylamine and 1-(5-methoxypyridin-3-yl)-1,5-pentanediol was employed to generate the 2-(pyridin-3-yl)-piperidine ring system in 69–72% yield. PMID:19320505

  15. Conjugate addition-enantioselective protonation reactions.

    PubMed

    Phelan, James P; Ellman, Jonathan A

    2016-01-01

    The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals.

  16. Gold(I)-catalyzed enantioselective cycloaddition reactions

    PubMed Central

    2013-01-01

    Summary In recent years there have been extraordinary developments of gold(I)-catalyzed enantioselective processes. This includes progress in the area of cycloaddition reactions, which are of particular interest due to their potential for the rapid construction of optically active cyclic products. In this article we will summarize some of the most remarkable examples, emphasizing reaction mechanisms and key intermediates involved in the processes. PMID:24204438

  17. Nonthermal Plasma Synthesis of Nanocrystals: Fundamental Principles, Materials, and Applications.

    PubMed

    Kortshagen, Uwe R; Sankaran, R Mohan; Pereira, Rui N; Girshick, Steven L; Wu, Jeslin J; Aydil, Eray S

    2016-09-28

    Nonthermal plasmas have emerged as a viable synthesis technique for nanocrystal materials. Inherently solvent and ligand-free, nonthermal plasmas offer the ability to synthesize high purity nanocrystals of materials that require high synthesis temperatures. The nonequilibrium environment in nonthermal plasmas has a number of attractive attributes: energetic surface reactions selectively heat the nanoparticles to temperatures that can strongly exceed the gas temperature; charging of nanoparticles through plasma electrons reduces or eliminates nanoparticle agglomeration; and the large difference between the chemical potentials of the gaseous growth species and the species bound to the nanoparticle surfaces facilitates nanocrystal doping. This paper reviews the state of the art in nonthermal plasma synthesis of nanocrystals. It discusses the fundamentals of nanocrystal formation in plasmas, reviews practical implementations of plasma reactors, surveys the materials that have been produced with nonthermal plasmas and surface chemistries that have been developed, and provides an overview of applications of plasma-synthesized nanocrystals.

  18. Nonthermal Plasma Synthesis of Nanocrystals: Fundamental Principles, Materials, and Applications.

    PubMed

    Kortshagen, Uwe R; Sankaran, R Mohan; Pereira, Rui N; Girshick, Steven L; Wu, Jeslin J; Aydil, Eray S

    2016-09-28

    Nonthermal plasmas have emerged as a viable synthesis technique for nanocrystal materials. Inherently solvent and ligand-free, nonthermal plasmas offer the ability to synthesize high purity nanocrystals of materials that require high synthesis temperatures. The nonequilibrium environment in nonthermal plasmas has a number of attractive attributes: energetic surface reactions selectively heat the nanoparticles to temperatures that can strongly exceed the gas temperature; charging of nanoparticles through plasma electrons reduces or eliminates nanoparticle agglomeration; and the large difference between the chemical potentials of the gaseous growth species and the species bound to the nanoparticle surfaces facilitates nanocrystal doping. This paper reviews the state of the art in nonthermal plasma synthesis of nanocrystals. It discusses the fundamentals of nanocrystal formation in plasmas, reviews practical implementations of plasma reactors, surveys the materials that have been produced with nonthermal plasmas and surface chemistries that have been developed, and provides an overview of applications of plasma-synthesized nanocrystals. PMID:27550744

  19. Sulfoxide-Based Enantioselective Nazarov Cyclization: Divergent Syntheses of (+)-Isopaucifloral F, (+)-Quadrangularin A, and (+)-Pallidol.

    PubMed

    Tang, Mei-Lin; Peng, Peng; Liu, Zheng-Yu; Zhang, Jian; Yu, Jian-Ming; Sun, Xun

    2016-10-01

    The synthesis of enantiomerically pure 3-aryl substituted indanones is developed using an enantioselective sulfoxide-based Knoevenagel condensation/Nazarov cyclization procedure. After the reductive desulfonation of the methyl para-tolyl sulfoxide-containing chiral auxiliary under mild conditions, selected enantiomerically pure indanone is used for the divergent total syntheses of three resveratrol natural products (+)-isopaucifloral F, (+)-quadrangularin A, and (+)-pallidol. PMID:27490335

  20. Organocatalytic, enantioselective, intramolecular oxa-Michael reaction of alkoxyboronate: a new strategy for enantioenriched 1-substituted 1,3-dihydroisobenzofurans.

    PubMed

    Ravindra, Barnala; Das, Braja Gopal; Ghorai, Prasanta

    2014-11-01

    An unprecedented strategy for the synthesis of enantioenriched 1-substituted 1,3-dihydroisobenzofurans via an enantioselective oxa-Michael reaction of o-alkoxyboronate containing chalcone (II) has been accomplished employing cinchona alkaloid based squaramide bifunctional organocatalyst in the presence of proton source. The corresponding alkoxyboronate intermediates have been readily prepared in situ from o-formyl chalcones using neutral borane as hydride source and a tertiary amine moiety which is a counterpart of the catalyst.

  1. Enantioselective Phytotoxicity of Imazamox Against Maize Seedlings.

    PubMed

    Wei, Jing; Zhang, Xiaoxiao; Li, Xuesheng; Zeng, Dongqiang; Tan, Huihua

    2016-02-01

    There is increasing concern about the enantioselective effects of chiral herbicides. To study the enantioselective toxicity of the chiral herbicide imazamox on maize, maize seedlings (Zhengda 619, Zea mays L.) were exposed to imazamox racemate and enantiomers in hydroponic experiments. The results showed that imazamox enantiomers selectively affected maize. The effective concentration of Rac-, S- and R-imazamox that caused 50 % inhibition after 5 days treatments (EC50,5d) were 0.4212, 1.2142 and 0.2460 mg L(-1), respectively, for maize root length; 0.0002, 0.1005, 0.0032 mg L(-1), respectively, for maize root fresh weight; 0.7114, 1.4056 and 0.4530 mg L(-1), respectively, for maize shoot height; 0.6220, 1.5418, 0.2286 mg L(-1), respectively, for maize shoot fresh weight; and 0.1100, 0.3306, 0.0307 mg L(-1), respectively, for the total chlorophyll content of leaves. The root morphological parameters and root activity reflected the toxicity effects in the order R-imazamox > Rac-imazamox > S-imazamox. Maize roots were more sensitive to imazamox than maize shoots. The chiral herbicide imazamox poses enantioselective phytotoxicity on maize seedlings: the order of toxicity is R-imazamox > Rac-imazamox > S-imazamox. PMID:26508428

  2. Synthesis of boron nitride nanotubes and their applications

    PubMed Central

    Kalay, Saban; Yilmaz, Zehra; Sen, Ozlem; Emanet, Melis; Kazanc, Emine

    2015-01-01

    Summary Boron nitride nanotubes (BNNTs) have been increasingly investigated for use in a wide range of applications due to their unique physicochemical properties including high hydrophobicity, heat and electrical insulation, resistance to oxidation, and hydrogen storage capacity. They are also valued for their possible medical and biomedical applications including drug delivery, use in biomaterials, and neutron capture therapy. In this review, BNNT synthesis methods and the surface modification strategies are first discussed, and then their toxicity and application studies are summarized. Finally, a perspective for the future use of these novel materials is discussed. PMID:25671154

  3. Controlling enantioselectivity in chiral capillary electrophoresis with inclusion-complexation.

    PubMed

    Fanali, S

    1997-12-19

    The separation of chiral compounds is of key importance in different fields of application, e.g., pharmaceutical, industrial, forensic, biological, clinical etc. Capillary electrophoresis (CE) is a powerful analytical method applied in chiral analysis and inclusion-complexation is one of the most frequently used mechanism to improve the selectivity of the enantiomeric separation. Cyclodextrins and their derivatives or modified crown-ethers have been successfully applied in CE for the enantiomeric separation of a wide number of analytes. This review surveys the separation of enantiomers by CE when chiral selectors, forming inclusion-complexation, are used. The control of enantioselectivity can be done carefully by considering several experimental parameters such as chiral selector type and concentration, pH, ionic strength and concentration of the background electrolyte, electroosmotic flow, organic modifier etc. The review presents a list of the latest separation of enantiomers by CE where inclusion-complexation plays a key role in the stereoselective separation mechanism.

  4. Waveform synthesis for imaging and ranging applications

    DOEpatents

    Doerry, Armin W.; Dudley, Peter A.; Dubert, Dale F.; Tise, Bertice L.

    2004-12-07

    Frequency dependent corrections are provided for quadrature imbalance and Local Oscillator (LO) feed-through. An operational procedure filters imbalance and LO feed-through effects without prior calibration or equalization. Waveform generation can be adjusted/corrected in a synthetic aperture radar system (SAR), where a rolling phase shift is applied to the SAR's QDWS signal where it is demodulated in a receiver; unwanted energies, such as LO feed-through and/or imbalance energy, are separated from a desired signal in Doppler; the separated energy is filtered from the receiver leaving the desired signal; and the separated energy in the receiver is measured to determine the degree of imbalance that is represented by it. Calibration methods can also be implemented into synthesis. The degree of LO feed-through and imbalance can be used to determine calibration values that can then be provided as compensation for frequency dependent errors in components, such as the QDWS and SSB mixer, affecting quadrature signal quality.

  5. Lipase-catalyzed highly enantioselective kinetic resolution of boron-containing chiral alcohols.

    PubMed

    Andrade, Leandro H; Barcellos, Thiago

    2009-07-16

    The first application of enzymes as catalysts to obtain optically pure boron compounds is described. The kinetic resolution of boron-containing chiral alcohols via enantioselective transesterification catalyzed by lipases was studied. Aromatic, allylic, and aliphatic secondary alcohols containing a boronate ester or boronic acid group were resolved by lipase from Candida antartica (CALB), and excellent E values (E > 200) and high enantiomeric excesses (up to >99%) of both remaining substrates and acetylated product were obtained. PMID:19552446

  6. Lipase-catalyzed highly enantioselective kinetic resolution of boron-containing chiral alcohols.

    PubMed

    Andrade, Leandro H; Barcellos, Thiago

    2009-07-16

    The first application of enzymes as catalysts to obtain optically pure boron compounds is described. The kinetic resolution of boron-containing chiral alcohols via enantioselective transesterification catalyzed by lipases was studied. Aromatic, allylic, and aliphatic secondary alcohols containing a boronate ester or boronic acid group were resolved by lipase from Candida antartica (CALB), and excellent E values (E > 200) and high enantiomeric excesses (up to >99%) of both remaining substrates and acetylated product were obtained.

  7. Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids.

    PubMed

    Song, Song; Zhu, Shou-Fei; Pu, Liu-Yang; Zhou, Qi-Lin

    2013-06-01

    Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF(-) =tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. PMID:23610004

  8. Palladium-Catalyzed Enantioselective 1,1-Fluoroarylation of Aminoalkenes

    PubMed Central

    2016-01-01

    The development of an enantioselective palladium-catalyzed 1,1-fluoroarylation of unactivated aminoalkenes is described. The reaction uses arylboronic acids as the arene source and Selectfluor as the fluorine source to generate benzylic fluorides in good yields with excellent enantioselectivities. This transformation, likely proceeding through an oxidative Heck mechanism, affords 1,1-difunctionalized alkene products. PMID:26378886

  9. Enantioselective Cycloaddition of Münchnones onto [60]Fullerene: Organocatalysis versus Metal Catalysis

    PubMed Central

    2014-01-01

    Novel chiral catalytic systems based on both organic compounds and metal salts have been developed for the enantioselective [3 + 2] cycloaddition of münchnones onto fullerenes and olefins. These two different approaches proved to be efficient and complementary in the synthesis of optically active pyrrolino[3,4:1,2][60]fullerenes with high levels of enantiomeric excess and moderate to good conversions. Further functionalization of the pyrrolinofullerene carboxylic acid derivatives has been carried out by esterification and amidation reactions. PMID:24483247

  10. Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams.

    PubMed

    Byrd, Katherine M

    2015-01-01

    The conjugate addition reaction has been a useful tool in the formation of carbon-carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams.

  11. Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

    PubMed Central

    2015-01-01

    Summary The conjugate addition reaction has been a useful tool in the formation of carbon–carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. PMID:25977728

  12. Nanoceria as Antioxidant: Synthesis and Biomedical Applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The therapeutic application of nanomaterials has been a focus of numerous studies in the past decade. Due to its unique redox properties, cerium oxide (ceria) is finding widespread use in the treatment of medical disorders caused by the reactive oxygen intermediates (ROI). The radical-scavenging rol...

  13. Synthesis of Fluorosurfactants for Emulsion-Based Biological Applications

    PubMed Central

    2015-01-01

    Microemulsion represents an attractive platform for fundamental and applied biomedical research because the emulsified droplets can serve as millions of compartmentalized micrometer-sized reactors amenable to high-throughput screening or online monitoring. However, establishing stable emulsions with surfactants that are compatible with biological applications remains a significant challenge. Motivated by the lack of commercially available surfactants suitable for microemulsion-based biological assays, this study describes the facile synthesis of a biocompatible fluorosurfactant with nonionic tris(hydroxymethyl)methyl (Tris) polar head groups. We have further demonstrated compatibility of the developed surfactant with diverse emulsion-based applications, including DNA polymeric nanoparticle synthesis, enzymatic activity assay, and bacterial or mammalian cell culture, in the setup of both double- and multiphases of emulsions. PMID:24646088

  14. Conducting Polymer Nanostructures: Template Synthesis and Applications in Energy Storage

    PubMed Central

    Pan, Lijia; Qiu, Hao; Dou, Chunmeng; Li, Yun; Pu, Lin; Xu, Jianbin; Shi, Yi

    2010-01-01

    Conducting polymer nanostructures have received increasing attention in both fundamental research and various application fields in recent decades. Compared with bulk conducting polymers, conducting polymer nanostructures are expected to display improved performance in energy storage because of the unique properties arising from their nanoscaled size: high electrical conductivity, large surface area, short path lengths for the transport of ions, and high electrochemical activity. Template methods are emerging for a sort of facile, efficient, and highly controllable synthesis of conducting polymer nanostructures. This paper reviews template synthesis routes for conducting polymer nanostructures, including soft and hard template methods, as well as its mechanisms. The application of conducting polymer mesostructures in energy storage devices, such as supercapacitors and rechargeable batteries, are discussed. PMID:20717527

  15. Chiral separation by enantioselective liquid-liquid extraction.

    PubMed

    Schuur, Boelo; Verkuijl, Bastiaan J V; Minnaard, Adriaan J; de Vries, Johannes G; Heeres, Hero J; Feringa, Ben L

    2011-01-01

    The literature on enantioselective liquid-liquid extraction (ELLE) spans more than half a century of research. Nonetheless, a comprehensive overview has not appeared during the past few decades. Enantioselective liquid-liquid extraction is a technology of interest for a wide range of chemists and chemical engineers in the fields of fine chemicals, pharmaceuticals, agrochemicals, fragrances and foods. In this review the principles and advances of resolution through enantioselective liquid-liquid extraction are discussed, starting with an introduction on the principles of enantioselective liquid-liquid extraction including host-guest chemistry, extraction and phase transfer mechanisms, and multistage liquid-liquid extraction processing. Then the literature on enantioselective liquid-liquid extraction systems is reviewed, structured on extractant classes. The following extractant classes are considered: crown ether based extractants, metal complexes and metalloids, extractants based on tartrates, and a final section with all other types of chiral extractants.

  16. Synthesis, properties, and applications of iron nanoparticles.

    SciTech Connect

    Huber, Dale L.

    2005-01-01

    Iron, the most ubiquitous of the transition metals and the fourth most plentiful element in the Earths crust, is the structural backbone of our modern infrastructure. It is therefore ironic that as a nanoparticle, iron has been somewhat neglected in favor of its own oxides, as well as other metals such as cobalt, nickel, gold, and platinum. This is unfortunate, but understandable. Irons reactivity is important in macroscopic applications (particularly rusting), but is a dominant concern at the nanoscale. Finely divided iron has long been known to be pyrophoric, which is a major reason that iron nanoparticles have not been more fully studied to date. This extreme reactivity has traditionally made iron nanoparticles difficult to study and inconvenient for practical applications. Iron however has a great deal to offer at the nanoscale, including very potent magnetic and catalytic properties. Recent work has begun to take advantage of irons potential, and work in this field appears to be blossoming.

  17. Electrospun metallic nanowires: Synthesis, characterization, and applications

    NASA Astrophysics Data System (ADS)

    Khalil, Abdullah; Singh Lalia, Boor; Hashaikeh, Raed; Khraisheh, Marwan

    2013-11-01

    Metals are known to have unique thermal, mechanical, electrical, and catalytic properties. On the other hand, metallic nanowires are promising materials for variety of applications such as transparent conductive film for photovoltaic devices, electrodes for batteries, as well as nano-reinforcement for composite materials. Whereas varieties of methods have been explored to synthesize metal nanowires with different characteristics, electrospinning has also been found to be successful for that purpose. Even though electrospinning of polymeric nanofibers is a well-established field, there are several challenges that need to be overcome to use the electrospinning technique for the fabrication of metallic nanowires. These challenges are mainly related to the multi-steps fabrication process and its relation to the structure evolution of the nanowires. In addition to reviewing the literature, this article identifies promising avenues for further research in this area with particular emphasis on the applications that nonwoven metal wires confined in a nano-scale can open.

  18. Cellulose nanocrystals: synthesis, functional properties, and applications.

    PubMed

    George, Johnsy; Sabapathi, S N

    2015-01-01

    Cellulose nanocrystals are unique nanomaterials derived from the most abundant and almost inexhaustible natural polymer, cellulose. These nanomaterials have received significant interest due to their mechanical, optical, chemical, and rheological properties. Cellulose nanocrystals primarily obtained from naturally occurring cellulose fibers are biodegradable and renewable in nature and hence they serve as a sustainable and environmentally friendly material for most applications. These nanocrystals are basically hydrophilic in nature; however, they can be surface functionalized to meet various challenging requirements, such as the development of high-performance nanocomposites, using hydrophobic polymer matrices. Considering the ever-increasing interdisciplinary research being carried out on cellulose nanocrystals, this review aims to collate the knowledge available about the sources, chemical structure, and physical and chemical isolation procedures, as well as describes the mechanical, optical, and rheological properties, of cellulose nanocrystals. Innovative applications in diverse fields such as biomedical engineering, material sciences, electronics, catalysis, etc, wherein these cellulose nanocrystals can be used, are highlighted. PMID:26604715

  19. Cellulose nanocrystals: synthesis, functional properties, and applications

    PubMed Central

    George, Johnsy; Sabapathi, SN

    2015-01-01

    Cellulose nanocrystals are unique nanomaterials derived from the most abundant and almost inexhaustible natural polymer, cellulose. These nanomaterials have received significant interest due to their mechanical, optical, chemical, and rheological properties. Cellulose nanocrystals primarily obtained from naturally occurring cellulose fibers are biodegradable and renewable in nature and hence they serve as a sustainable and environmentally friendly material for most applications. These nanocrystals are basically hydrophilic in nature; however, they can be surface functionalized to meet various challenging requirements, such as the development of high-performance nanocomposites, using hydrophobic polymer matrices. Considering the ever-increasing interdisciplinary research being carried out on cellulose nanocrystals, this review aims to collate the knowledge available about the sources, chemical structure, and physical and chemical isolation procedures, as well as describes the mechanical, optical, and rheological properties, of cellulose nanocrystals. Innovative applications in diverse fields such as biomedical engineering, material sciences, electronics, catalysis, etc, wherein these cellulose nanocrystals can be used, are highlighted. PMID:26604715

  20. Plasma Synthesis of Nanoparticles for Nanocomposite Energy Applications

    SciTech Connect

    Peter C. Kong; Alex W. Kawczak

    2008-09-01

    The nanocomposite energy applications for plasma reactor produced nanoparticles are reviewed. Nanoparticles are commonly defined as particles less than 100 nm in diameter. Due to this small size, nanoparticles have a high surface-to-volume ratio. This increases the surface energy compared to the bulk material. The high surface-to-volume ratio and size effects (quantum effects) give nanoparticles distinctive chemical, electronic, optical, magnetic and mechanical properties from those of the bulk material. Nanoparticles synthesis can be grouped into 3 broad approaches. The first one is wet phase synthesis (sol-gel processing), the second is mechanical attrition, and the third is gas-phase synthesis (aerosol). The properties of the final product may differ significantly depending on the fabrication route. Currently, there are no economical large-scale production processes for nanoparticles. This hinders the widespread applications of nanomaterials in products. The Idaho National Laboratory (INL) is engaging in research and development of advanced modular hybrid plasma reactors for low cost production of nanoparticles that is predicted to accelerate application research and enable the formation of technology innovation alliances that will result in the commercial production of nanocomposites for alternative energy production devices such as fuel cells, photovoltaics and electrochemical double layer capacitors.

  1. An enantioselective strategy for the total synthesis of (S)-tylophorine via catalytic asymmetric allylation and a one-pot DMAP-promoted isocyanate formation/Lewis acid catalyzed cyclization sequence.

    PubMed

    Su, Bo; Zhang, Hui; Deng, Meng; Wang, Qingmin

    2014-06-14

    A new asymmetric total synthesis of a phenanthroindolizidine alkaloid (S)-tylophorine is reported, which features a catalytic asymmetric allylation of aldehydes and an unexpected one-pot DMAP promoted isocyanate formation and Lewis acid catalyzed intramolecular cyclization reaction. In addition, White's direct C-H oxidation catalyst system converting monosubstituted olefins to linear allylic acetates was also employed for late-stage transformation.

  2. Gold Nanocages: From Synthesis to Theranostic Applications

    PubMed Central

    XIA, YOUNAN; LI, WEIYANG; COBLEY, CLAIRE M.; CHEN, JINGYI; XIA, XIAOHU; ZHANG, QIANG; YANG, MIAOXIN; CHO, EUN CHUL; BROWN, PAIGE K.

    2011-01-01

    CONSPECTUS Gold nanostructures have garnered considerable attention in recent years for their potential to enhance both the diagnosis and treatment of cancer through their advantageous chemical and physical properties. The key feature of Au nanostructures for enabling this diverse array of biomedical applications is their attractive optical properties, i.e. the scattering and absorption of light at resonant wavelengths due to the excitation of plasmon oscillations. This phenomenon is commonly known as localized surface plasmon resonance (LSPR) and is the source of the ruby red color of conventional Au colloids. The resonant wavelength is highly dependent on the size, shape, and geometry of the nanostructures, providing a set of knobs to maneuver the optical properties as needed. For in vivo applications, especially when optical excitation or transduction is involved, the LSPR peaks of the Au nanostructures have to be tuned to the transparent window of soft tissues in the near-infrared (NIR) region (from 700–900 nm) in order to maximize the penetration depth. One class of nanostructures with tunable LSPR peaks in the NIR region is Au nanocages. These versatile nanostructures are characterized by hollow interiors, ultrathin and porous walls, and can be prepared in relatively large quantities using a remarkably simple procedure based on the galvanic replacement between Ag nanocubes and aqueous chloroauric acid. The LSPR peaks of Au nanocages can be readily and precisely tuned to any wavelength in the NIR region by controlling their size and/or wall thickness. Other significant features of Au nanocages that make them particularly intriguing materials for biomedical applications include their compact sizes, large absorption cross sections (almost five orders of magnitude greater than those of conventional organic dyes), bio-inertness, as well as a robust and straightforward procedure for surface modification based on the Au-thiolate chemistry. In this article, we

  3. Silver nanoparticles: synthesis, properties, and therapeutic applications

    PubMed Central

    Wei, Liuya; Lu, Jingran; Xu, Huizhong; Patel, Atish; Chen, Zhe-Sheng; Chen, Guofang

    2014-01-01

    Silver nanoparticles (AgNPs) have been widely used in biomedical fields because of their intrinsic therapeutic properties. Here, we introduce methods of synthesizing AgNPs and discuss their physicochemical, localized surface plasmon resonance (LSPR) and toxicity properties. We also review the impact of AgNPs on human health and the environment along with the underlying mechanisms. More importantly, we highlight the newly emerging applications of AgNPs as antiviral agents, photosensitizers and/or radiosensitizers, and anticancer therapeutic agents in the treatment of leukemia, breast cancer, hepatocellular carcinoma, lung cancer, and skin and/or oral carcinoma. PMID:25543008

  4. One‐Dimensional Ferroelectric Nanostructures: Synthesis, Properties, and Applications

    PubMed Central

    Liang, Longyue; Kang, Xueliang

    2016-01-01

    One‐dimensional (1D) ferroelectric nanostructures, such as nanowires, nanorods, nanotubes, nanobelts, and nanofibers, have been studied with increasing intensity in recent years. Because of their excellent ferroelectric, ferroelastic, pyroelectric, piezoelectric, inverse piezoelectric, ferroelectric‐photovoltaic (FE‐PV), and other unique physical properties, 1D ferroelectric nanostructures have been widely used in energy‐harvesting devices, nonvolatile random access memory applications, nanoelectromechanical systems, advanced sensors, FE‐PV devices, and photocatalysis mechanisms. This review summarizes the current state of 1D ferroelectric nanostructures and provides an overview of the synthesis methods, properties, and practical applications of 1D nanostructures. Finally, the prospects for future investigations are outlined. PMID:27812477

  5. [Progress in synthesis technologies and application of aviation biofuels].

    PubMed

    Sun, Xiaoying; Liu, Xiang; Zhao, Xuebing; Yang, Ming; Liu, Dehua

    2013-03-01

    Development of aviation biofuels has attracted great attention worldwide because that the shortage of fossil resources has become more and more serious. In the present paper, the development background, synthesis technologies, current application status and existing problems of aviation biofuels were reviewed. Several preparation routes of aviation biofuels were described, including Fischer-Tropsch process, catalytic hydrogenation and catalytic cracking of bio-oil. The status of flight tests and commercial operation were also introduced. Finally the problems for development and application of aviation biofuels were stated, and some accommodation were proposed.

  6. Boron Nitride Nanotube: Synthesis and Applications

    NASA Technical Reports Server (NTRS)

    Tiano, Amanda L.; Park, Cheol; Lee, Joseph W.; Luong, Hoa H.; Gibbons, Luke J.; Chu, Sang-Hyon; Applin, Samantha I.; Gnoffo, Peter; Lowther, Sharon; Kim, Hyun Jung; Danehy, Paul M.; Inman, Jennifer A.; Jones, Stephen B.; Kang, Jin Ho; Sauti, Godfrey; Thibeault, Sheila A.; Yamakov, Vesselin; Wise, Kristopher E.; Su, Ji; Fay, Catharine C.

    2014-01-01

    Scientists have predicted that carbon's immediate neighbors on the periodic chart, boron and nitrogen, may also form perfect nanotubes, since the advent of carbon nanotubes (CNTs) in 1991. First proposed then synthesized by researchers at UC Berkeley in the mid 1990's, the boron nitride nanotube (BNNT) has proven very difficult to make until now. Herein we provide an update on a catalyst-free method for synthesizing highly crystalline, small diameter BNNTs with a high aspect ratio using a high power laser under a high pressure and high temperature environment first discovered jointly by NASA/NIA JSA. Progress in purification methods, dispersion studies, BNNT mat and composite formation, and modeling and diagnostics will also be presented. The white BNNTs offer extraordinary properties including neutron radiation shielding, piezoelectricity, thermal oxidative stability (> 800 C in air), mechanical strength, and toughness. The characteristics of the novel BNNTs and BNNT polymer composites and their potential applications are discussed.

  7. Engineering and Applications of fungal laccases for organic synthesis

    PubMed Central

    Kunamneni, Adinarayana; Camarero, Susana; García-Burgos, Carlos; Plou, Francisco J; Ballesteros, Antonio; Alcalde, Miguel

    2008-01-01

    Laccases are multi-copper containing oxidases (EC 1.10.3.2), widely distributed in fungi, higher plants and bacteria. Laccase catalyses the oxidation of phenols, polyphenols and anilines by one-electron abstraction, with the concomitant reduction of oxygen to water in a four-electron transfer process. In the presence of small redox mediators, laccase offers a broader repertory of oxidations including non-phenolic substrates. Hence, fungal laccases are considered as ideal green catalysts of great biotechnological impact due to their few requirements (they only require air, and they produce water as the only by-product) and their broad substrate specificity, including direct bioelectrocatalysis. Thus, laccases and/or laccase-mediator systems find potential applications in bioremediation, paper pulp bleaching, finishing of textiles, bio-fuel cells and more. Significantly, laccases can be used in organic synthesis, as they can perform exquisite transformations ranging from the oxidation of functional groups to the heteromolecular coupling for production of new antibiotics derivatives, or the catalysis of key steps in the synthesis of complex natural products. In this review, the application of fungal laccases and their engineering by rational design and directed evolution for organic synthesis purposes are discussed. PMID:19019256

  8. Enantioselective, continuous (R)- and (S)-2-butanol synthesis: achieving high space-time yields with recombinant E. coli cells in a micro-aqueous, solvent-free reaction system.

    PubMed

    Erdmann, Vanessa; Mackfeld, Ursula; Rother, Dörte; Jakoblinnert, Andre

    2014-12-10

    The stereoselective production of (R)- or (S)-2-butanol is highly challenging. A potent synthesis strategy is the biocatalytic asymmetric reduction of 2-butanone applying alcohol dehydrogenases. However, due to a time-dependent racemisation process, high stereoselectivity is only obtained at incomplete conversion after short reaction times. Here, we present a solution to this problem: by using a continuous process, high biocatalytic selectivity can be achieved while racemisation is suppressed successfully. Furthermore, high conversion was achieved by applying recombinant, lyophilised E. coli cells hosting Lactobacillus brevis alcohol dehydrogenase in a micro-aqueous solvent-free continuous reaction system. The optimisation of residence time (τ) and 2-butanone concentration boosted both conversion (>99%) and enantiomeric excess (ee) of (R)-2-butanol (>96%). When a residence time of only τ=3.1 min was applied, productivity was extraordinary with a space-time yield of 2278±29g/(L×d), thus exceeding the highest values reported to date by a factor of more than eight. The use of E. coli cells overexpressing an ADH of complementary stereoselectivity yielded a synthesis strategy for (S)-2-butanol with an excellent ee (>98%). Although conversion was only moderate (up to 46%), excellent space-time yields of up to 461g/(L×d) were achieved. The investigated concept represents a synthesis strategy that can also be applied to other biocatalytic processes where racemisation poses a challenge.

  9. High enantioselective Novozym 435-catalyzed esterification of (R,S)-flurbiprofen monitored with a chiral stationary phase.

    PubMed

    Siódmiak, Tomasz; Mangelings, Debby; Vander Heyden, Yvan; Ziegler-Borowska, Marta; Marszałł, Michał Piotr

    2015-03-01

    Lipases form Candida rugosa and Candida antarctica were tested for their application in the enzymatic kinetic resolution of (R,S)-flurbiprofen by enantioselective esterification. Successful chromatographic separation with well-resolved peaks of (R)- and (S)-flurbiprofen and their esters was achieved in one run on chiral stationary phases by high-performance liquid chromatography (HPLC). In this study screening of enzymes was performed, and Novozym 435 was selected as an optimal catalyst for obtaining products with high enantiopurity. Additionally, the influence of organic solvents (dichloromethane, dichloroethane, dichloropropane, and methyl tert-butyl ether), primary alcohols (methanol, ethanol, n-propanol, and n-butanol), reaction time, and temperature on the enantiomeric ratio and conversion was tested. The high values of enantiomeric ratio (E in the range of 51.3-90.5) of the esterification of (R,S)-flurbiprofen were obtained for all tested alcohols using Novozym 435, which have a great significance in the field of biotechnological synthesis of drugs. The optimal temperature range for the performed reactions was from 37 to 45 °C. As a result of the optimization, (R)-flurbiprofen methyl ester was obtained with a high optical purity, eep = 96.3 %, after 96 h of incubation. The enantiomeric ratio of the reaction was E = 90.5 and conversion was C = 35.7 %.

  10. Gold nanocages: synthesis, properties, and applications.

    PubMed

    Skrabalak, Sara E; Chen, Jingyi; Sun, Yugang; Lu, Xianmao; Au, Leslie; Cobley, Claire M; Xia, Younan

    2008-12-01

    Noble-metal nanocages comprise a novel class of nanostructures possessing hollow interiors and porous walls. They are prepared using a remarkably simple galvanic replacement reaction between solutions containing metal precursor salts and Ag nanostructures prepared through polyol reduction. The electrochemical potential difference between the two species drives the reaction, with the reduced metal depositing on the surface of the Ag nanostructure. In our most studied example, involving HAuCl(4) as the metal precursor, the resultant Au is deposited epitaxially on the surface of the Ag nanocubes, adopting their underlying cubic form. Concurrent with this deposition, the interior Ag is oxidized and removed, together with alloying and dealloying, to produce hollow and, eventually, porous structures that we commonly refer to as Au nanocages. This approach is versatile, with a wide range of morphologies (e.g., nanorings, prism-shaped nanoboxes, nanotubes, and multiple-walled nanoshells or nanotubes) available upon changing the shape of the initial Ag template. In addition to Au-based structures, switching the metal salt precursors to Na(2)PtCl(4) and Na(2)PdCl(4) allows for the preparation of Pt- and Pd-containing hollow nanostructures, respectively. We have found that changing the amount of metal precursor added to the suspension of Ag nanocubes is a simple means of tuning both the composition and the localized surface plasmon resonance (LSPR) of the metal nanocages. Using this approach, we are developing structures for biomedical and catalytic applications. Because discrete dipole approximations predicted that the Au nanocages would have large absorption cross-sections and because their LSPR can be tuned into the near-infrared (where the attenuation of light by blood and soft tissue is greatly reduced), they are attractive materials for biomedical applications in which the selective absorption of light at great depths is desirable. For example, we have explored their

  11. Design, synthesis, and evaluation of materials for microelectronics applications

    NASA Astrophysics Data System (ADS)

    Heath, William Hoy

    The advancement of the microelectronics industry is heavily dependent on the design, synthesis, and integration of new materials. Non-chemically amplified photoresists (NCAR) consist of a base resin and photoactive additive which inhibits the dissolution of the this resin. The robustness of NCARs has made them well suited to the unique material requirements of the photomask making industry for many years. However, smaller feature sizes now require mask makers to move to shorter wavelengths of light and thus a more transparent polymer and photoactive compound are needed for these applications. During the search for 157nm photoresists, it was found that polymers containing the hexafluoroisopropanol functionality are transparent well into the ultraviolet region and possess dissolution characteristics similar to the Novolak resins utilized in NCARs. A suitable photoactive compound (PAC) has been identified; the synthesis of the PAC and transparent polymers, as well as their formulation, dissolution properties, and lithographic evaluation will be presented. Additionally, the base catalyzed imidization of poly(amic acid ethyl ester) (PAETE) provides a good tool for developing a photosensitive polyimide insulator. However few base photogenerators (PBG) exist that absorb at the appropriate wavelength (>400nm) for use in these opaque films. Two sensitized systems were evaluated; their synthesis, photophysical evaluation, and attempted imaging in PAETE will be described. Additionally, the synthesis and photophysical evaluation of a red-shifted thiophene-based PBG will be described. Finally, step and flash imprint lithography exhibits a great promise as a cost effective alternative imaging solution to traditional optical lithography. A strippable resist is needed to preserve the templates used in this process should they become contaminated. The thermal reversibility of urethanes, specifically those derived from aromatic oximes, make them well suited for integration into a

  12. Enantioselective cellular uptake of chiral semiconductor nanocrystals

    NASA Astrophysics Data System (ADS)

    Martynenko, I. V.; Kuznetsova, V. A.; Litvinov, I. K.; Orlova, A. O.; Maslov, V. G.; Fedorov, A. V.; Dubavik, A.; Purcell-Milton, F.; Gun'ko, Yu K.; Baranov, A. V.

    2016-02-01

    The influence of the chirality of semiconductor nanocrystals, CdSe/ZnS quantum dots (QDs) capped with L- and D-cysteine, on the efficiency of their uptake by living Ehrlich Ascite carcinoma cells is studied by spectral- and time-resolved fluorescence microspectroscopy. We report an evident enantioselective process where cellular uptake of the L-Cys QDs is almost twice as effective as that of the D-Cys QDs. This finding paves the way for the creation of novel approaches to control the biological properties and behavior of nanomaterials in living cells.

  13. Conjugate addition-enantioselective protonation reactions.

    PubMed

    Phelan, James P; Ellman, Jonathan A

    2016-01-01

    The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. PMID:27559372

  14. Conjugate addition–enantioselective protonation reactions

    PubMed Central

    Phelan, James P

    2016-01-01

    Summary The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. PMID:27559372

  15. Conjugated microporous polymers: design, synthesis and application.

    PubMed

    Xu, Yanhong; Jin, Shangbin; Xu, Hong; Nagai, Atsushi; Jiang, Donglin

    2013-10-21

    Conjugated microporous polymers (CMPs) are a class of organic porous polymers that combine π-conjugated skeletons with permanent nanopores, in sharp contrast to other porous materials that are not π-conjugated and with conventional conjugated polymers that are nonporous. As an emerging material platform, CMPs offer a high flexibility for the molecular design of conjugated skeletons and nanopores. Various chemical reactions, building blocks and synthetic methods have been developed and a broad variety of CMPs with different structures and specific properties have been synthesized, driving the rapid growth of the field. CMPs are unique in that they allow the complementary utilization of π-conjugated skeletons and nanopores for functional exploration; they have shown great potential for challenging energy and environmental issues, as exemplified by their excellent performance in gas adsorption, heterogeneous catalysis, light emitting, light harvesting and electrical energy storage. This review describes the molecular design principles of CMPs, advancements in synthetic and structural studies and the frontiers of functional exploration and potential applications.

  16. Synthesis and catalytic applications of combined zeolitic/mesoporous materials

    PubMed Central

    Vernimmen, Jarian; Cool, Pegie

    2011-01-01

    Summary In the last decade, research concerning nanoporous siliceous materials has been focused on mesoporous materials with intrinsic zeolitic features. These materials are thought to be superior, because they are able to combine (i) the enhanced diffusion and accessibility for larger molecules and viscous fluids typical of mesoporous materials with (ii) the remarkable stability, catalytic activity and selectivity of zeolites. This review gives an overview of the state of the art concerning combined zeolitic/mesoporous materials. Focus is put on the synthesis and the applications of the combined zeolitic/mesoporous materials. The different synthesis approaches and formation mechanisms leading to these materials are comprehensively discussed and compared. Moreover, Ti-containing nanoporous materials as redox catalysts are discussed to illustrate a potential implementation of combined zeolitic/mesoporous materials. PMID:22259762

  17. Six-Membered Aromatic Polyazides: Synthesis and Application.

    PubMed

    Chapyshev, Sergei V

    2015-10-21

    Aromatic polyazides are widely used as starting materials in organic synthesis and photochemical studies, as well as photoresists in microelectronics and as cross-linking agents in polymer chemistry. Some aromatic polyazides possess high antitumor activity, while many others are of considerable interest as high-energy materials and precursors of high-spin nitrenes and C₃N₄ carbon nitride nanomaterials. The use of aromatic polyazides in click-reactions may be a new promising direction in the design of various supramolecular systems possessing interesting chemical, physical and biological properties. This review is devoted to the synthesis, properties and applications of six-membered aromatic compounds containing three and more azido groups in the ring.

  18. Functional Metal Oxide Nanostructures: Their Synthesis, Characterization, and Energy Applications

    NASA Astrophysics Data System (ADS)

    Iyer, Aparna

    This research focuses on studying metal oxides (MnO 2, Co3O4, MgO, Y2O3) for various applications including water oxidation and photocatalytic oxidation, developing different synthesis methodologies, and presenting detailed characterization studies of these metal oxides. This research consists of three major parts. The first part is studying novel applications and developing a synthesis method for manganese oxide nanomaterials. Manganese oxide materials were studied for renewable energy applications by using them as catalysts for water oxidation reactions. In this study, various crystallographic forms of manganese oxides (amorphous, 2D layered, 1D 2 x 2 tunnel structures) were evaluated for water oxidation catalysis. Amorphous manganese oxides (AMO) were found to be catalytically active for chemical and photochemical water oxidation compared to cryptomelane type tunnel manganese oxides (2 x 2 tunnels; OMS2) or layered birnessite (OL-1) materials. Detailed characterization was done to establish a correlation between the properties of the manganese oxide materials and their catalytic activities in water oxidation. The gas phase photocatalytic oxidation of 2-propanol under visible light was studied using manganese oxide 2 x 2 tunnel structures (OMS-2) as catalysts (Chapter 3). The reaction is 100% selective to acetone. As suggested by the photocatalytic and characterization data, important factors for the design of active OMS-2 photocatalysts are synthesis methodology, morphology, mixed valency and the release of oxygen from the OMS-2 structure. Manganese oxide octahedral molecular sieves (2 x 2 tunnels; OMS-2) with self-assembled dense or hollow sphere morphologies were fabricated via a room temperature ultrasonic atomization assisted synthesis (Chapter 4). The properties and catalytic activities of these newly developed materials were compared with that of OMS-2 synthesized by conventional reflux route. These materials exhibit exceptionally high catalytic activities

  19. Enantioselective Construction of Pyrrolidines by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Imines

    PubMed Central

    Trost, Barry M.; Silverman, Steven M.

    2012-01-01

    A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo-, and enantioselectivity. Use of a diphenylazetidine ligand allows the complimentary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters. PMID:22309214

  20. The Significance of Degenerate Processes to Enantioselective Olefin Metathesis Reactions Promoted by Stereogenic-at-Mo Complexes

    PubMed Central

    Meek, Simon J.; Malcolmson, Steven J.; Li, Bo; Schrock, Richard R.; Hoveyda, Amir H.

    2009-01-01

    The present study provides spectroscopic and experimental evidence demonstrating that degenerate metathesis is critical to the effectiveness of this emerging class of chiral catalysts. Isolation and characterization (X-ray) of both diastereomeric complexes, as well as examination of the reactivity and enantioselectivity patterns exhibited by such initiating neophylidenes in promoting RCM processes, are disclosed. Only when sufficient amounts of ethylene are generated and inversion at Mo through degenerate processes occurs at a sufficiently rapid rate, is high enantioselectivity achieved, irrespective of the stereochemical identity of the initiating alkylidene (Curtin-Hammett kinetics). With diastereomeric metal complexes that undergo rapid interconversion, stereomutation at the metal center becomes inconsequential and stereoselective synthesis of a chiral catalyst is not required. PMID:19842640

  1. Enantioselective silyl protection of alcohols catalysed by an amino-acid-based small molecule.

    PubMed

    Zhao, Yu; Rodrigo, Jason; Hoveyda, Amir H; Snapper, Marc L

    2006-09-01

    Reliable, selective and environmentally friendly chemical transformations are crucial to the development of new therapeutics and the design of novel materials. Chiral catalysts that can be easily prepared and used to obtain organic molecules of high enantiomeric purity are critical to modern chemical synthesis. The development of protecting groups that shield reactive functionalities has also proved indispensable in the preparation of complex biologically active molecules. Here we present a chiral catalyst that promotes the enantioselective protection of a secondary alcohol as one of the most commonly used protected forms of an alcohol: a silyl ether. The catalyst is a small, simple molecule that can be prepared in three steps from commercial materials without the need for rigorously controlled conditions. Enantioselective silylations are performed with commercial silyl chlorides and produce yields of up to 96 per cent at an enantiomeric ratio of up to 98:2. Chiral catalysts for selective formation of commonly used protecting groups such as silyl ethers should significantly enhance the ability of chemical synthesis to deliver, in a more practical and efficient manner, important organic molecules.

  2. Enantioselective Construction of Remote Quaternary Stereocenters

    PubMed Central

    Mei, Tian-Sheng; Patel, Harshkumar H.; Sigman, Matthew S.

    2014-01-01

    Summary Molecules containing all-carbon quaternary stereocenters – carbon atoms bonded to four distinct carbon substituents – are prevalent in Nature. However, the construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for forging quaternary stereocenters that are remote from other functional groups are underdeveloped. Herein we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids. The reported method allows direct access to quaternary all-carbon-substituted β-, γ-, δ-, ε- or ζ aryl carbonyl compounds, as the unsaturation of the alkene is relayed to the alcohol resulting in the formation of a carbonyl group. The scope of the process also includes incorporation of pre-existing stereocenters along the alkyl chain, which links the alkene and the alcohol, wherein the stereocenter is preserved. The described method is flexible, allowing access to diverse building blocks containing an enantiomerically enriched, quaternary center. PMID:24717439

  3. Synthesis and biomedical applications of aerogels: Possibilities and challenges.

    PubMed

    Maleki, Hajar; Durães, Luisa; García-González, Carlos A; Del Gaudio, Pasquale; Portugal, António; Mahmoudi, Morteza

    2016-10-01

    Aerogels are an exceptional group of nanoporous materials with outstanding physicochemical properties. Due to their unique physical, chemical, and mechanical properties, aerogels are recognized as promising candidates for diverse applications including, thermal insulation, catalysis, environmental cleaning up, chemical sensors, acoustic transducers, energy storage devices, metal casting molds and water repellant coatings. Here, we have provided a comprehensive overview on the synthesis, processing and drying methods of the mostly investigated types of aerogels used in the biological and biomedical contexts, including silica aerogels, silica-polymer composites, polymeric and biopolymer aerogels. In addition, the very recent challenges on these aerogels with regard to their applicability in biomedical field as well as for personalized medicine applications are considered and explained in detail.

  4. Synthesis and biomedical applications of aerogels: Possibilities and challenges.

    PubMed

    Maleki, Hajar; Durães, Luisa; García-González, Carlos A; Del Gaudio, Pasquale; Portugal, António; Mahmoudi, Morteza

    2016-10-01

    Aerogels are an exceptional group of nanoporous materials with outstanding physicochemical properties. Due to their unique physical, chemical, and mechanical properties, aerogels are recognized as promising candidates for diverse applications including, thermal insulation, catalysis, environmental cleaning up, chemical sensors, acoustic transducers, energy storage devices, metal casting molds and water repellant coatings. Here, we have provided a comprehensive overview on the synthesis, processing and drying methods of the mostly investigated types of aerogels used in the biological and biomedical contexts, including silica aerogels, silica-polymer composites, polymeric and biopolymer aerogels. In addition, the very recent challenges on these aerogels with regard to their applicability in biomedical field as well as for personalized medicine applications are considered and explained in detail. PMID:27321857

  5. Synthesis, Characterization and Application Of PbS Quantum Dots

    SciTech Connect

    Sarma, Sweety; Datta, Pranayee; Barua, Kishore Kr.; Karmakar, Sanjib

    2009-06-29

    Lead Chalcogenides (PbS, PbSe, PbTe) quantum dots (QDs) are ideal for fundamental studies of strongly quantum confined systems with possible technological applications. Tunable electronic transitions at near--infrared wavelengths can be obtained with these QDs. Applications of lead chalcogenides encompass quite a good number of important field viz. the fields of telecommunications, medical electronics, optoelectronics etc. Very recently, it has been proposed that 'memristor'(Memory resistor) can be realized in nanoscale systems with coupled ionic and electronic transports. The hystersis characteristics of 'memristor' are observed in many nanoscale electronic devices including semiconductor quantum dot devices. This paper reports synthesis of PbS QDs by chemical route. The fabricated samples are characterized by UV-Vis, XRD, SEM, TEM, EDS, etc. Observed characteristics confirm nano formation. I-V characteristics of the sample are studied for investigating their applications as 'memristor'.

  6. Asymmetric organic/metal(oxide) hybrid nanoparticles: synthesis and applications

    NASA Astrophysics Data System (ADS)

    He, Jie; Liu, Yijing; Hood, Taylor C.; Zhang, Peng; Gong, Jinlong; Nie, Zhihong

    2013-05-01

    Asymmetric particles (APs) with broken centrosymmetry are of great interest, due to the asymmetric surface properties and diverse functionalities. In particular, organic/metal(oxide) APs naturally combine the significantly different and complementary properties of organic and inorganic species, leading to their unique applications in various fields. In this review article, we highlighted recent advances in the synthesis and applications of organic/metal(oxide) APs. This type of APs is grounded on chemical or physical interactions between metal(oxide) NPs and organic small molecular or polymeric ligands. The synthetic methodologies were summarized in three categories, including the selective surface modifications, phase separation of mixed ligands on the surface of metal(oxide) NPs, and direct synthesis of APs. We further discussed the unique applications of organic/metal(oxide) APs in self-assembly, sensors, catalysis, and biomedicine, as a result of the distinctions between asymmetrically distributed organic and inorganic components. Finally, challenges and future directions are discussed in an outlook section.

  7. Peptide protected gold clusters: chemical synthesis and biomedical applications

    NASA Astrophysics Data System (ADS)

    Yuan, Qing; Wang, Yaling; Zhao, Lina; Liu, Ru; Gao, Fuping; Gao, Liang; Gao, Xueyun

    2016-06-01

    Bridging the gap between atoms and nanoparticles, noble metal clusters with atomic precision continue to attract considerable attention due to their important applications in catalysis, energy transformation, biosensing and biomedicine. Greatly different to common chemical synthesis, a one-step biomimetic synthesis of peptide-conjugated metal clusters has been developed to meet the demand of emerging bioapplications. Under mild conditions, multifunctional peptides containing metal capturing, reactive and targeting groups are rationally designed and elaborately synthesized to fabricate atomically precise peptide protected metal clusters. Among them, peptide-protected Au Cs (peptide-Au Cs) possess a great deal of exceptional advantages such as nanometer dimensions, high photostability, good biocompatibility, accurate chemical formula and specific protein targeting capacity. In this review article, we focus on the recent advances in potential theranostic fields by introducing the rising progress of peptide-Au Cs for biological imaging, biological analysis and therapeutic applications. The interactions between Au Cs and biological systems as well as potential mechanisms are also our concerned theme. We expect that the rapidly growing interest in Au Cs-based theranostic applications will attract broader concerns across various disciplines.

  8. Asymmetric organic/metal(oxide) hybrid nanoparticles: synthesis and applications.

    PubMed

    He, Jie; Liu, Yijing; Hood, Taylor C; Zhang, Peng; Gong, Jinlong; Nie, Zhihong

    2013-06-21

    Asymmetric particles (APs) with broken centrosymmetry are of great interest, due to the asymmetric surface properties and diverse functionalities. In particular, organic/metal(oxide) APs naturally combine the significantly different and complementary properties of organic and inorganic species, leading to their unique applications in various fields. In this review article, we highlighted recent advances in the synthesis and applications of organic/metal(oxide) APs. This type of APs is grounded on chemical or physical interactions between metal(oxide) NPs and organic small molecular or polymeric ligands. The synthetic methodologies were summarized in three categories, including the selective surface modifications, phase separation of mixed ligands on the surface of metal(oxide) NPs, and direct synthesis of APs. We further discussed the unique applications of organic/metal(oxide) APs in self-assembly, sensors, catalysis, and biomedicine, as a result of the distinctions between asymmetrically distributed organic and inorganic components. Finally, challenges and future directions are discussed in an outlook section.

  9. Synthesis of 5-bromopyridyl-2-magnesium chloride and its application in the synthesis of functionalized pyridines.

    PubMed

    Song, Jinhua J; Yee, Nathan K; Tan, Zhulin; Xu, Jinghua; Kapadia, Suresh R; Senanayake, Chris H

    2004-12-23

    [reaction: see text] The 5-bromopyridyl-2-magnesium chloride (2), which was not accessible previously, was efficiently synthesized for the first time via an iodo-magnesium exchange reaction with 5-bromo-2-iodopyridine (1). This reactive intermediate was allowed to react with a variety of electrophiles to afford a range of useful functionalized pyridine derivatives. Application of this methodology to 5-bromo-2-iodo-3-picoline provided a simple and economical synthesis of a key intermediate for the preparation of Lonafarnib, a potent anticancer agent.

  10. Enantioselective synthesis of planar-chiral ferrocene-fused 4-pyridones and their application in construction of pyridine-based organocatalyst library.

    PubMed

    Ogasawara, Masamichi; Wada, Shiro; Isshiki, Erika; Kamimura, Takumi; Yanagisawa, Akira; Takahashi, Tamotsu; Yoshida, Kazuhiro

    2015-05-01

    A couple of planar-chiral ferrocene-fused 4-pyridone derivatives 2a and 2b were synthesized in enantiomerically pure form by scalable asymmetric transformations. Pyridones 2 are versatile precursors to various ferrocene-fused pyridine derivatives, which are useful nucleophilic asymmetric organocatalysts. PMID:25893666

  11. Enantioselective synthesis of planar-chiral ferrocene-fused 4-pyridones and their application in construction of pyridine-based organocatalyst library.

    PubMed

    Ogasawara, Masamichi; Wada, Shiro; Isshiki, Erika; Kamimura, Takumi; Yanagisawa, Akira; Takahashi, Tamotsu; Yoshida, Kazuhiro

    2015-05-01

    A couple of planar-chiral ferrocene-fused 4-pyridone derivatives 2a and 2b were synthesized in enantiomerically pure form by scalable asymmetric transformations. Pyridones 2 are versatile precursors to various ferrocene-fused pyridine derivatives, which are useful nucleophilic asymmetric organocatalysts.

  12. Applications of C–H Functionalization Logic to Cyclobutane Synthesis

    PubMed Central

    2015-01-01

    The application of C–H functionalization logic to target-oriented synthesis provides an exciting new venue for the development of new and useful strategies in organic chemistry. In this article, C–H functionalization reactions are explored as an alternative approach to access pseudodimeric cyclobutane natural products, such as the dictazole and the piperarborenine families. The use of these strategies in a variety of complex settings highlights the subtle geometric, steric, and electronic effects at play in the auxiliary guided C–H functionalization of cyclobutanes. PMID:24548142

  13. Controlled synthesis of porous platinum nanostructures for catalytic applications.

    PubMed

    Cao, Yanqin; Zhang, Junwei; Yang, Yong; Huang, Zhengren; Long, Nguyen Viet; Nogami, Masayuki

    2014-02-01

    Porous platinum, that has outstanding catalytic and electrical properties and superior resistant characteristics to corrosion, has been widely applied in chemical, petrochemical, pharmaceutical, electronic, and automotive industries. As the catalytic activity and selectivity depend on the size, shape and structure of nanomaterials, the strategies for controlling these factors of platinum nanomaterials to get excellent catalytic properties are discussed. Here, recent advances in the design and preparation of various porous platinum nanostructures are reviewed, including wet-chemical synthesis, electro-deposition, galvanic replacement reaction and de-alloying technology. The applications of various platinum nanostructures are also discussed, especially in fuel cells. PMID:24749422

  14. Synthesis and characterization of zinc oxide nanostructures for piezoelectric applications

    NASA Astrophysics Data System (ADS)

    Hughes, William L.

    Union between top-down and bottom-up assembly is inevitable when scaling down physical, chemical, and biological sensors and probes. Current sensor/probe-based technologies are firmly founded on top-down manufacturing, with limitations in cost of production, manufacturing methods, and material constraints. As an alternative to such limitations, contemporary synthesis techniques for one-dimensional nanostructures have been combined with established methods of micro-fabrication for the development of novel tools and techniques for nanotechnology. More specifically, this dissertation is a systematic study of the synthesis and characterization of ZnO nanostructures for piezoelectric applications. Within this study the following goals have been achieved: (1) rational design and control of a diversity of novel ZnO nanostructures, (2) improved understanding of polar-surface-dominated (PSD) phenomena among Wurtzite crystal structures, (3) confirmation of Tasker's Rule via the synthesis, characterization, and modeling of polar-surface-dominated nanostructures, (4) measurement of the surface-charge density for real polar surfaces of ZnO, (5) confirmation of the electrostatic polar-charge model used to describe polar-surface-dominated phenomena, (6) dispersion of ZnO nanobelts onto the selective layers of surface acoustic wave (SAW) devices for gas sensing applications, (7) manipulation of ZnO nanostructures using an atomic force microscope (AFM) for the development of piezoelectric devices, (8) fabrication of bulk acoustic resonator (BAR) and film bulk acoustic resonator (FBAR) devices based on the integrity of individual ZnO belts, (9) electrical characterization of a ZnO belt BAR device, (10) prediction and confirmation of the electrical response from a BAR device using a one-dimensional Krimholt-Leedom-Matthaei (KLM) model, and (11) development of a finite element model (FEM) to accurately predict the electrical response from ZnO belt BAR and FBAR devices in 3D.

  15. Salen Promoted Enantioselective Nazarov Cyclizations of Activated and Unactivated Dienones

    PubMed Central

    2013-01-01

    A novel class of chiral 5,5′-di(2,4,6-trialkyl)aryl salen-metal complexes have been developed and shown to catalyze highly enantioselective Nazarov cyclization reactions, giving rise to cyclopentenoids in 90:10–98:2 er. Significantly, the catalysts also promote, for the first time, highly enantioselective Nazarov reactions of “unactivated” dienones, producing hydrindenone products having in place three contiguous chiral centers. PMID:23506509

  16. Enantioselective Biotransformation of Chiral PCBs in Whole Poplar Plants

    PubMed Central

    Zhai, Guangshu; Hu, Dingfei; Lehmler, Hans-Joachim; Schnoor, Jerald L.

    2011-01-01

    Chiral PCBs have been used as molecular probes of biological metabolic processes due to their special physical, chemical and biological properties. Many animal studies showed the enantioselective biotransformation of chiral PCBs, but it is unclear whether plants can enantioselectively biotransform chiral PCBs. In order to explore the enantioselectivity of chiral PCBs in whole plants, poplars (Populus deltoides × nigra, DN34), a model plant with complete genomic sequence, were hydroponically exposed to 2,2′,3,5′,6-pentachlorobiphenyl (PCB95) and 2,2′,3,3′,6,6′-hexachlorobiphenyl (PCB136) for 20 days. PCB95 and PCB136 were shown to be absorbed, taken-up and translocated in whole poplars, and they were detected in various tissues of whole poplars. However, the enantioselectivity of poplar for PCB95 and PCB136 proved to be quite different. The first eluting enantiomer of PCB95 was enantioselectively removed in whole poplar, especially in the middle and bottom xylem. It was likely enantioselectively metabolized inside poplar tissues, in contrast to racemic mixtures of PCB95 remaining in hydroponic solutions in contact with plant roots of whole and dead poplars. Unlike PCB95, PCB136 remained nearly racemic in most parts of whole poplars after 20 days exposure. These results suggest that PCB136 is more difficult to be enantioslectively biotransformed than PCB95 in whole poplars. This is the first evidence of enantioselectivity of chiral PCBs in whole plants, and suggests that poplars can enantioselectively biotransform at least one chiral PCB. PMID:21329345

  17. Enantioselective α-Benzylation of Aldehydes via Photoredox Organocatalysis

    PubMed Central

    Shih, Hui-Wen; Vander Wal, Mark N.; Grange, Rebecca L.; MacMillan, David W. C.

    2011-01-01

    The first enantioselective aldehyde α-benzylation using electron-deficient aryl and heteroaryl substrates has been accomplished. The productive merger of a chiral imidazolidinone organocatalyst and a commercially available iridium photoredox catalyst in the presence of household fluorescent light directly affords the desired homobenzylic stereogenicity in good to excellent yield and enantioselectivity. The utility of this methodology has been demonstrated via rapid access to an enantioen-riched drug target for angiogenesis suppression. PMID:20831195

  18. Enantioselective Nazarov Cyclization Catalyzed by a Cinchona Alkaloid Derivative

    PubMed Central

    Huang, Yu-Wen; Frontier, Alison J.

    2015-01-01

    Nucleophilic catalysts for a 1,6 addition/Nazarov cyclization/elimination sequence were evaluated for their ability to induce enantioselectivity in the electrocyclization step. Of the tertiary amines examined, it was found that a cinchona alkaloid derivative was able to generate substituted 5-hydroxy γ-methylene cyclopentenones with excellent enantioselectivity. The study results suggest that successful cyclization depends upon the ability of the dienyl diketone substrate to readily adopt an s-cis conformation. PMID:26085696

  19. Soft chemical synthesis of silicon nanosheets and their applications

    NASA Astrophysics Data System (ADS)

    Nakano, Hideyuki; Ikuno, Takashi

    2016-12-01

    Two-dimensional silicon nanomaterials are expected to show different properties from those of bulk silicon materials by virtue of surface functionalization and quantum size effects. Since facile fabrication processes of large area silicon nanosheets (SiNSs) are required for practical applications, a development of soft chemical synthesis route without using conventional vacuum processes is a challenging issue. We have recently succeeded to prepare SiNSs with sub-nanometer thicknesses by exfoliating layered silicon compounds, and they are found to be composed of crystalline single-atom-thick silicon layers. In this review, we present the synthesis and modification methods of SiNSs. These SiNSs have atomically flat and smooth surfaces due to dense coverage of organic moieties, and they are easily self-assembled in a concentrated state to form a regularly stacked structure. We have also characterized the electron transport properties and the electronic structures of SiNSs. Finally, the potential applications of these SiNSs and organic modified SiNSs are also reviewed.

  20. Nanocrystals-Related Synthesis, Assembly, and Energy Applications

    SciTech Connect

    Zou, Bo; Yu, Williams; Seo, Jaetae; Zhu, Ting; Hu, Michael Z.

    2012-01-01

    During the past decades, nanocrystals have attracted broad attention due to their unique shape- and size-dependent physical and chemical properties that differ drastically from their bulk counterparts. Hitherto, much effort has been dedicated to achieving rational controlling over the morphology, assembly, and related energy applications of the nanomaterials. Therefore, the ability to manipulate the morphology, size, and size distribution of inorganic nanomaterials is still an important goal in modern materials physics and chemistry. Especially, the world s demand for energy supply is causing a dramatic escalation of social and political unrest. Likewise, the environmental impact of the global climate change due to the combustion of fossil fuel is becoming increasingly alarming. These problems compel us to search for effective routes to build devices that can supply sustainable energy, with not only high efficiency but also environmental friendship. One of ways to relieve the energy crisis is to exploit devices based on renewable energy sources, such as solar energy and water power. Aiming at this exploration, the primary stage requires the design of appropriate strategies for the synthesis of high-quality nanocrystals with respect to size uniformity and superior electrochemical performances. As a consequence, we organize the current special issue for Journal of Nanomaterials to provide the authors with a platform and readers with the latest achievements of nanocrystals-related synthesis, assembly, and energy applications.

  1. Anisotropic metal nanoparticles: Synthesis, assembly, and optical applications.

    PubMed

    Murphy, Catherine J; Sau, Tapan K; Gole, Anand M; Orendorff, Christopher J; Gao, Jinxin; Gou, Linfeng; Hunyadi, Simona E; Li, Tan

    2005-07-28

    This feature article highlights work from the authors' laboratories on the synthesis, assembly, reactivity, and optical applications of metallic nanoparticles of nonspherical shape, especially nanorods. The synthesis is a seed-mediated growth procedure, in which metal salts are reduced initially with a strong reducing agent, in water, to produce approximately 4 nm seed particles. Subsequent reduction of more metal salt with a weak reducing agent, in the presence of structure-directing additives, leads to the controlled formation of nanorods of specified aspect ratio and can also yield other shapes of nanoparticles (stars, tetrapods, blocks, cubes, etc.). Variations in reaction conditions and crystallographic analysis of gold nanorods have led to insight into the growth mechanism of these materials. Assembly of nanorods can be driven by simple evaporation from solution or by rational design with molecular-scale connectors. Short nanorods appear to be more chemically reactive than long nanorods. Finally, optical applications in sensing and imaging, which take advantage of the visible light absorption and scattering properties of the nanorods, are discussed. PMID:16852739

  2. Semiconducting black phosphorus: synthesis, transport properties and electronic applications.

    PubMed

    Liu, Han; Du, Yuchen; Deng, Yexin; Ye, Peide D

    2015-05-01

    Phosphorus is one of the most abundant elements preserved in earth, and it comprises a fraction of ∼0.1% of the earth crust. In general, phosphorus has several allotropes, and the two most commonly seen allotropes, i.e. white and red phosphorus, are widely used in explosives and safety matches. In addition, black phosphorus, though rarely mentioned, is a layered semiconductor and has great potential in optical and electronic applications. Remarkably, this layered material can be reduced to one single atomic layer in the vertical direction owing to the van der Waals structure, and is known as phosphorene, in which the physical properties can be tremendously different from its bulk counterpart. In this review article, we trace back to the research history on black phosphorus of over 100 years from the synthesis to material properties, and extend the topic from black phosphorus to phosphorene. The physical and transport properties are highlighted for further applications in electronic and optoelectronics devices.

  3. Aerosol Route Synthesis and Applications of Doped Nanostructured Materials

    NASA Astrophysics Data System (ADS)

    Sahu, Manoranjan

    Nanotechnology presents an attractive opportunity to address various challenges in air and water purification, energy, and other environment issues. Thus, the development of new nanoscale materials in low-cost scalable synthesis processes is important. Furthermore, the ability to independently manipulate the material properties as well as characterize the material at different steps along the synthesis route will aide in product optimization. In addition, to ensure safe and sustainable development of nanotechnology applications, potential impacts need to be evaluated. In this study, nanomaterial synthesis in a single-step gas phase reactor to continuously produce doped metal oxides was demonstrated. Copper-doped TiO2 nanomaterial properties (composition, size, and crystal phase) were independently controlled based on nanoparticle formation and growth mechanisms dictated by process control parameters. Copper dopant found to significantly affect TiO2 properties such as particle size, crystal phase, stability in the suspension, and absorption spectrum (shift from UV to visible light absorption). The in-situ charge distribution characterization of the synthesized nanomaterials was carried out by integrating a tandem differential mobility analyzer (TDMA) set up with the flame reactor synthesis system. Both singly- and doubly- charged nanoparticles were measured, with the charged fractions dependent on particle mobility and dopant concentration. A theoretical calculation was conducted to evaluate the relative importance of the two charging mechanisms, diffusion and thermo-ionization, in the flame. Nanoparticle exposure characterization was conducted during synthesis as a function of operating condition, product recovery and handling technique, and during maintenance of the reactors. Strategies were then indentified to minimize the exposure risk. The nanoparticle exposure potential varied depending on the operating conditions such as precursor feed rate, working

  4. Carbon nanotubes from synthesis to in vivo biomedical applications.

    PubMed

    Sajid, Muhammad Imran; Jamshaid, Usama; Jamshaid, Talha; Zafar, Nadiah; Fessi, H; Elaissari, Abdelhamid

    2016-03-30

    Owing to their unique and interesting properties, extensive research round the globe has been carried out on carbon nanotubes and carbon nanotubes based systems to investigate their practical usefulness in biomedical applications. The results from these studies demonstrate a great promise in their use in targeted drug delivery systems, diagnostic techniques and in bio-analytical applications. Although, carbon nanotubes possess quite interesting properties, which make them potential candidates in the biomedical science, but they also have some inherent properties which arise great concern regarding their biosafety. In this comprehensive review, we have discussed different aspects of carbon nanotubes and carbon nanotube based systems related to biomedical applications. In the beginning, a short historical account of these tiny yet powerful particles is given followed by discussion regarding their types, properties, methods of synthesis, large scale production method, purification techniques and characterization aspects of carbon nanotubes. In the second part of the review, the functionalization of carbon nanotubes is reviewed in detail, which is not only important to make them biocompatible and stable in biological systems but also render them a great property of loading various biomolecules, diagnostic and therapeutic moieties resulting in diversified applications. In the final part of the review, emphasis is given on the pharmacokinetic aspects of carbon nanotubes including administration routes, absorption mechanisms, distribution and elimination of carbon nanotubes based systems. Lastly, a comprehensive account about the potential biomedical applications has been given followed by insights into the future.

  5. Synthesis and Applications of Non-spherical Dimer Colloids

    NASA Astrophysics Data System (ADS)

    Yoon, Kisun

    Colloids are promising building blocks in material synthesis because of their controllability of size and surface properties. The synthesis of chemically and/or geometrically anisotropic colloidal particles has received attentions with the expectation of building blocks for complex structures. However, the synthesis of anisotropic colloidal particles is by far more difficult than the synthesis of spherical colloidal particles. Lack of monodispersity and productivity of many anisotropic particles often limits their applications as a building block for complex structures. Thus, it is highly desirable to develop methods which can produce a large amount of monodisperse non-spherical particles with controllable asymmetric surface properties. This dissertation details the work for developing such a method. The major result of this dissertation is a synthetic method to produce monodisperse non-spherical colloids with anisotropic surface property in a large quantity. The anisotropic colloid, which we call it as Dimer particle, has two fused lobes like a dumbbell and each lobe's size can be independently controlled. We present a novel method to synthesize sub-micron size Dimer particles. This method can produce a large amount of submicron-sized Dimer particles with good monodispersity and well-controlled shape. Submicron-sized Dimer particles have been highly desired since they can be used as a building block for self assembly using Brownian motion, colloidal surfactant for Pickering emulsion, and photonic materials. To fully take advantage of the anisotropy of the particles, we develop a facile method to tailor the surface property of each lobe independently by asymmetrically coating the particles with gold nanoparticles. This method doesn't need the arrangement of particles onto any type of interfaces. Asymmetric coating of gold nanoparticles can be carried out simply by mixing Dimer particles with gold nanoparticles. The formation mechanism of the submicron-sized Dimer

  6. Improvement of enantioselectivity of the B-type halohydrin hydrogen-halide-lyase from Corynebacterium sp. N-1074.

    PubMed

    Watanabe, Fumiaki; Yu, Fujio; Ohtaki, Akashi; Yamanaka, Yasuaki; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi

    2016-09-01

    Halohydrin hydrogen-halide-lyase (H-Lyase) is a bacterial enzyme involved in the degradation of halohydrins. This enzyme catalyzes the intramolecular nucleophilic displacement of a halogen by a vicinal hydroxyl group in halohydrins, producing the corresponding epoxides. The H-Lyases have been classified into A, B and C subtypes based on amino acid sequence similarities. These enzymes have attracted much attention as industrial catalysts in the synthesis of chiral chemicals from prochiral halohydrins. In the present study, we constructed mutants of B-type H-Lyase from Corynebacterium sp. N-1074 (HheB) displaying higher enantioselectivity by structure-based site-directed mutagenesis and random mutagenesis. A triple mutant of HheB exhibited 98.5% enantioselectivity, the highest ever reported, toward (R)-4-chloro-3-hydroxy-butyronitrile production, with the yield reaching approximately two-fold that of the wild-type enzyme. We discuss the structural basis of the high enantioselectivity and productivity of the mutant by comparing the crystal structures of the mutant HheB and the wild-type enzyme in complex with or without the substrate analogue.

  7. Improvement of enantioselectivity of the B-type halohydrin hydrogen-halide-lyase from Corynebacterium sp. N-1074.

    PubMed

    Watanabe, Fumiaki; Yu, Fujio; Ohtaki, Akashi; Yamanaka, Yasuaki; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi

    2016-09-01

    Halohydrin hydrogen-halide-lyase (H-Lyase) is a bacterial enzyme involved in the degradation of halohydrins. This enzyme catalyzes the intramolecular nucleophilic displacement of a halogen by a vicinal hydroxyl group in halohydrins, producing the corresponding epoxides. The H-Lyases have been classified into A, B and C subtypes based on amino acid sequence similarities. These enzymes have attracted much attention as industrial catalysts in the synthesis of chiral chemicals from prochiral halohydrins. In the present study, we constructed mutants of B-type H-Lyase from Corynebacterium sp. N-1074 (HheB) displaying higher enantioselectivity by structure-based site-directed mutagenesis and random mutagenesis. A triple mutant of HheB exhibited 98.5% enantioselectivity, the highest ever reported, toward (R)-4-chloro-3-hydroxy-butyronitrile production, with the yield reaching approximately two-fold that of the wild-type enzyme. We discuss the structural basis of the high enantioselectivity and productivity of the mutant by comparing the crystal structures of the mutant HheB and the wild-type enzyme in complex with or without the substrate analogue. PMID:27215832

  8. Expanding the scope of Metal-Free enantioselective allylic substitutions: Anthrones

    PubMed Central

    Ceban, Victor; Tauchman, Jiří; Meazza, Marta; Gallagher, Greg; Light, Mark E.; Gergelitsová, Ivana; Veselý, Jan; Rios, Ramon

    2015-01-01

    The highly enantioselective asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with anthrones is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and excellent enantioselectivities. PMID:26592555

  9. Synthesis and applications of {sup 13}C glycerol

    SciTech Connect

    Stocking, E.; Khalsa, O.; Martinez, R.A.; Silks, L.A. III

    1994-12-01

    Due in part to the use of labeled glycerol for the {sup 13}C enrichment of biomolecules, we are currently developing new synthetic routes to various isotopomers of glycerol. Judging from our experience, traditional methods of glycerol synthesis are not easily adapted for isotopic enrichment and/or have poor overall yields (12 to 15%). Furthermore, the use of glycerol for enrichment can be prohibitively expensive and its availability is limited by the level of demand. We are presently developing a short de novo synthesis of glycerol from carbon dioxide ({approximately}53% overall yield for four steps) and are examining the feasibility of synthesizing site-specific {sup 13}C-labeled glycerol and dihydroxyacetone (DHA) from labeled methanol and carbon dioxide. One application of {sup 13}C glycerol we have examined is enzymatic conversion of glycerol to glyceraldehyde-3-monophosphate or dihydroxyacetone monophosphate (DHAP) with yields ranging from 25 to 50% (as determined by NMR spectroscopy). We are also pursuing the chemical conversion of {sup 13}C-labeled DHA to DHAP. We are especially interested in {sup 13}C-labeled DHAP because we are investigating its use as a chemo-enzymatic precursor for both labeled 2-deoxyribose and 2-deoxyribonucleic acids.

  10. Chiral metallohelical complexes enantioselectively target amyloid β for treating Alzheimer's disease.

    PubMed

    Li, Meng; Howson, Suzanne E; Dong, Kai; Gao, Nan; Ren, Jinsong; Scott, Peter; Qu, Xiaogang

    2014-08-20

    Stereochemistry is a very important issue for the pharmaceutical industry and can determine drug efficacy. The design and synthesis of small molecules, especially chiral molecules, which selectively target and inhibit amyloid-β (Aβ) aggregation, represent valid therapeutic strategies for treatment of Alzheimer's disease (AD). Herein we report that two triple-helical dinuclear metallosupramolecular complexes can act as a novel class of chiral amyloid-β inhibitors. Through targeting α/β-discordant stretches at the early steps of aggregation, these metal complexes can enantioselectively inhibit Aβ aggregation, which is demonstrated using fluorescent living cell-based screening and multiple biophysical and biochemical approaches. To the best of our knowledge, this is the first report of enantioselective inhibition of Aβ aggregation. Intriguingly, as a promising candidate for AD treatment, the chiral metal complex can cross the blood-brain barrier and have superoxide dismutase activity. It is well-known that chiral discrimination is important for understanding chiral drug action. Generally, one enantiomer is pharmaceutically active while the other is inactive or exerts severe side effects. Chiral discrimination should be important for AD treatment. Our work provides new insights into chiral inhibition of Aβ aggregation and opens a new avenue for design and screening of chiral agents as Aβ inhibitors against AD. PMID:25062433

  11. Direct and Highly Regioselective and Enantioselective Allylation of β-Diketones

    PubMed Central

    Chalifoux, Wesley A.; Reznik, Samuel K.; Leighton, James L.

    2012-01-01

    The enantioselective allylation of ketones represents both a problem of fundamental importance in asymmetric reaction design and one of only a very small number of available methods to access valuable tertiary carbinols. Despite the vast amount of attention from chemists that this problem has elicited,1-8 however, success has generally been limited to just a few simple ketone types thus limiting the utility of these methods. A method for the selective allylation of functionally complex ketones would be expected to increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective, and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by the co-optation of their enol form to provide the necessary Brønsted acid activation. This unprecedented reaction thus not only significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed, but also overturns more than a century of received wisdom regarding the reactivity of β-diketones. PMID:22763452

  12. Optimization of Serratia marcescens lipase production for enantioselective hydrolysis of 3-phenylglycidic acid ester.

    PubMed

    Gao, Li; Xu, Jian-He; Li, Xin-Jun; Liu, Zuo-Zhen

    2004-12-01

    Lipase production and cell growth of Serratia marcescens ECU1010 were optimized in shake flasks, with lipase production being enhanced 9.5-fold (4,780 U/l) compared with the initial activity (500 U/l). Optimal carbon and nitrogen sources were Tween-80 and peptone, and the optimal ratio of Tween-80 to peptone was 1:3. The optimized cultivation conditions were 25 degrees C and pH 6.5. Lipase activity, particularly specific activity, could be improved by decreasing the cultivation temperature from 35 to 25 degrees C. Enzyme stability was significantly improved by simple immobilization with synthetic adsorption resin no. 8244. After five reaction cycles, enzyme activity decreased only very slightly, while enantioselectivity of the preparation remained constant, and the ees (enantiomeric excess of the remaining substrate) achieved in all cases was higher than 97%. The resin-8244-lipase preparation can be used for efficient enantioselective hydrolysis of trans-3-(4'-methoxyphenyl)glycidic acid methyl ester [(+/-)-MPGM], a key intermediate in the synthesis of Diltiazem.

  13. Mechanistic Analysis and Optimization of the Copper-Catalyzed Enantioselective Intramolecular Alkene Aminooxygenation

    PubMed Central

    Paderes, Monissa C.; Keister, Jerome B.; Chemler, Sherry R.

    2013-01-01

    The catalytic asymmetric aminooxygenation of alkenes provides an efficient and straightforward approach to prepare chiral vicinal amino alcohols. We have reported a copper(II)-catalyzed enantioselective intramolecular alkene aminooxygenation, using (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as the oxygen source, which results in the synthesis of chiral indolines and pyrrolidines. Herein we disclose that kinetics studies indicate the reaction is first order both in substrate and the [Cu(R,R)-Ph-bis(oxazoline)]OTf2 catalyst, and zero order in TEMPO. Furthermore, kinetic isotope effect studies support that the cis aminocupration step, the addition of N-Cu across the alkene, is the rate-limiting step. Subsequent formation of a carbon radical intermediate, and direct carbon radical trapping with TEMPO is the indicated mechanism for the C-O bond formation as suggested by a deuterium labeling experiment. A ligand screen revealed that C(4)-phenyl substitution on the bis(oxazoline) is optimal for high asymmetric induction. The size of the substrate’s N-sulfonyl group also influences the enantioselectivity of the reaction. The preparative scale catalytic aminooxygenation reaction (gram scale) was demonstrated and an unexpected dependence on reaction temperature was uncovered on the larger scale reaction. PMID:23244027

  14. Mechanistic analysis and optimization of the copper-catalyzed enantioselective intramolecular alkene aminooxygenation.

    PubMed

    Paderes, Monissa C; Keister, Jerome B; Chemler, Sherry R

    2013-01-18

    The catalytic asymmetric aminooxygenation of alkenes provides an efficient and straightforward approach to prepare chiral vicinal amino alcohols. We have reported a copper(II)-catalyzed enantioselective intramolecular alkene aminooxygenation, using (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as the oxygen source, which results in the synthesis of chiral indolines and pyrrolidines. Herein we disclose that kinetics studies indicate the reaction is first order both in substrate and the [Cu(R,R)-Ph-bis(oxazoline)]OTf(2) catalyst and zero order in TEMPO. Furthermore, kinetic isotope effect studies support that the cis-aminocupration step, the addition of N-Cu across the alkene, is the rate-limiting step. Subsequent formation of a carbon radical intermediate and direct carbon radical trapping with TEMPO is the indicated mechanism for the C-O bond formation as suggested by a deuterium labeling experiment. A ligand screen revealed that C(4)-phenyl substitution on the bis(oxazoline) is optimal for high asymmetric induction. The size of the substrate's N-sulfonyl group also influences the enantioselectivity of the reaction. The preparative-scale catalytic aminooxygenation reaction (gram scale) was demonstrated, and an unexpected dependence on reaction temperature was uncovered on the larger scale reaction. PMID:23244027

  15. Adaptation of a Small-Molecule Hydrogen-Bond Donor Catalyst to an Enantioselective Hetero-Diels–Alder Reaction Hypothesized for Brevianamide Biosynthesis

    PubMed Central

    2015-01-01

    Chiral diamine-derived hydrogen-bond donors were evaluated for their ability to effect stereocontrol in an intramolecular hetero-Diels–Alder (HDA) reaction hypothesized in the biosynthesis of brevianamides A and B. Collectively, these results provide proof of principle that small-molecule hydrogen-bond catalysis, if even based on a hypothetical biosynthesis construct, holds significant potential within enantioselective natural product synthesis. PMID:25697748

  16. Nanoparticles for hyperthermic therapy: synthesis strategies and applications in glioblastoma

    PubMed Central

    Verma, Jyoti; Lal, Sumit; Van Noorden, Cornelis JF

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. Current GBM treatment includes surgery, radiation therapy, and chemotherapy, sometimes supplemented with novel therapies. Despite recent advances, survival of GBM patients remains poor. Major challenges in GBM treatment are drug delivery across the blood–brain barrier, restriction of damage to healthy brain tissues, and limitation of resistance to therapies. This article reviews recent advances in the application of magnetic nanoparticles (MNPs), gold nanorods (GNRs), and carbon nanotubes (CNTs) for hyperthermia ablation of GBM. First, the article introduces GBM, its current treatment, and hyperthermia as a potential modality for the management of GBM. Second, it introduces MNPs, GNRs, and CNTs as inorganic agents to induce hyperthermia in GBM. Third, it discusses different methodologies for synthesis of each inorganic agent. Finally, it reviews in vitro and in vivo studies in which MNPs, GNRs, and CNTs have been applied for hyperthermia ablation and drug delivery in GBM. PMID:24959075

  17. Arthrobacter sp. lipase immobilization for improvement in stability and enantioselectivity.

    PubMed

    Chaubey, Asha; Parshad, Rajinder; Koul, Surrinder; Taneja, Subhash C; Qazi, Ghulam N

    2006-12-01

    Arthrobacter sp. lipase (ABL, MTCC no. 5125) is being recognized as an efficient enzyme for the resolution of drugs and their intermediates. The immobilization of ABL on various matrices for its enantioselectivity, stability, and reusability has been studied. Immobilization by covalent bonding on sepharose and silica afforded a maximum of 380 and 40 IU/g activity, respectively, whereas sol-gel entrapment provided a maximum of 150 IU/g activity in dry powder. The immobilized enzyme displayed excellent stability in the pH range of 4-10 and even at higher temperature, i.e., 50-60 degrees C, compared to free enzyme, which is unstable under extreme conditions. The resolution of racemic auxiliaries like 1-phenyl ethanol and an intermediate of antidepressant drug fluoxetine, i.e., ethyl 3-hydroxy-3-phenylpropanoate alkyl acylates, provided exclusively R-(+) products ( approximately 99% ee, E=646 and 473), compared to cell free extract/whole cells which gave a product with approximately 96% ee (E=106 and 150). The repeated use (ten times) of covalently immobilized and entrapped ABL resulted in no loss in activity, thus demonstrating its prospects for commercial applications. PMID:16896604

  18. Enantioselective Recognition in Solution: The Case of Countercurrent Chromatography

    NASA Astrophysics Data System (ADS)

    Rubio, Núria; Minguillón, Cristina

    Countercurrent chromatography (CCC) is a preparative separation technique that works with a liquid stationary phase. Biphasic liquid systems are needed to perform a separation. Since a chiral selector is required to perform enantiomer separations, special requirements are imposed in CCC. The chiral selector (CS) must be located in the stationary phase since partitioning with the mobile phase would cause losses of the valuable chiral selector in the mobile phase. Sulfated cyclodextrins and proteins were used as polar CS located in the polar stationary phase (reversed phase mode). Apolar CSs such as N-dodecyl-L-proline 3,5-dimethylanilide or Whelk-O selectors, quinine and quinidine derivatives, cellulose or amylose apolar derivatives were used located in the apolar stationary phase (normal phase mode). The special CCC displacement method called pH-zone refining was found useful in the increase of the loading capacity for cellulose, quinine, quinidine, and proline-derived selectors. Dual and multidual mode uses of CCC could produce an increase in peak separation thereby broadening the applicability of moderately enantioselective CSs.

  19. Crystalline colloidal array hydrogel materials: From synthesis to applications

    NASA Astrophysics Data System (ADS)

    Liu, Lei

    This dissertation is focused on the synthesis, characterization, and applications of crystalline colloidal array (CCA) hydrogel materials. CCA are three dimensional periodic structures formed by the electrostatic self-assembly of monodisperse macroionic colloidal spheres in an aqueous medium. CCA dispersions efficiently Bragg diffract light in the near UV to near IR spectral region, and are useful in areas of optical device fabrication, chemical sensing devices, and novel separation materials. We developed methodologies to synthesize monodisperse colloidal silica spheres via hydrolysis and condensation of tetraethoxysilane in nonionic reverse microemulsion systems. We examined the effects of reaction parameters and surfactant hydrophilic-lipophilic-balance (HLB) number on the final particle size and size distribution. We developed a unique multi-step growth technique by which the final particle diameter can be continuously selected with extremely narrow size distributions over a broad size range. We also developed methodologies to surface functionalize silica spheres to increase the particle surface charge density by two orders of magnitude. The resulting dispersions readily self-assemble into CCA and Bragg diffract light over a broad concentration range. In addition, we discovered an anomalously intense secondary diffraction phenomenon from CCA which occurs due to the superimposed Bragg diffraction from numerous lattice planes. This was quantitatively modeled by using dynamical diffraction and light scattering theory. We extended the microemulsion synthesis methodologies to fabricate monodisperse SiOsb2/CdS composite spheres with well-controlled and complex morphologies. By controlling the co-precipitation process, CdS could be incorporated into silica spheres as quantum dots, as large inclusions, as surface patches and welds, or as shells or cores. Further processing of these materials by selectively etching out CdS templates also generated a series of porous

  20. Synthesis and characterization of aqueous quantum dots for biomedical applications

    NASA Astrophysics Data System (ADS)

    Li, Hui

    Quantum Dots (QDs) are semiconductor nanocrystals (1˜20 nm) exhibiting distinctive photoluminescence (PL) properties due to the quantum confinement effect. Having many advantages over organic dyes, such as broad excitation and resistance to photobleaching, QDs are widely used in bioapplications as one of most exciting nanobiotechnologies. To date, most commercial QDs are synthesized through the traditional organometallic method and contain toxic elements, such as cadmium, lead, mercury, arsenic, etc. The overall goal of this thesis study is to develop an aqueous synthesis method to produce nontoxic quantum dots with strong emission and good stability, suitable for biomedical imaging applications. Firstly, an aqueous, simple, environmentally friendly synthesis method was developed. With cadmium sulfide (CdS) QDs as an example system, various processing parameters and capping molecules were examined to improve the synthesis and optimize the PL properties. The obtained water soluble QDs exhibited ultra small size (˜5 nm), strong PL and good stability. Thereafter, using the aqueous method, the zinc sulfide (ZnS) QDs were synthesized with different capping molecules, i.e., 3-mercaptopropionic acid (MPA) and 3-(mercaptopropyl)trimethoxysilane (MPS). Especially, via a newly developed capping molecule replacement method, the present ZnS QDs exhibited bright blue emission with a quantum yield of 75% and more than 60 days lifetime in the ambient conditions. Two cytotoxicity tests with human endothelial cells verified the nontoxicity of the ZnS QDs by cell counting with Trypan blue staining and fluorescence assay with Alamar Blue. Taking advantage of the versatile surface chemistry, several strategies were explored to conjugate the water soluble QDs with biomolecules, i.e., antibody and streptavidin. Accordingly, the imaging of Salmonella t. cells and biotinylated microbeads has been successfully demonstrated. In addition, polyethylenimine (PEI)-QDs complex was formed and

  1. Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches.

    PubMed

    Zhang, Xi-Feng; Liu, Zhi-Guo; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. PMID:27649147

  2. Anisotropic gold nanoparticles: synthesis, properties, applications, and toxicity.

    PubMed

    Li, Na; Zhao, Pengxiang; Astruc, Didier

    2014-02-10

    Anisotropic gold nanoparticles (AuNPs) have attracted the interest of scientists for over a century, but research in this field has considerably accelerated since 2000 with the synthesis of numerous 1D, 2D, and 3D shapes as well as hollow AuNP structures. The anisotropy of these nonspherical, hollow, and nanoshell AuNP structures is the source of the plasmon absorption in the visible region as well as in the near-infrared (NIR) region. This NIR absorption is especially sensitive to the AuNP shape and medium and can be shifted towards the part of the NIR region in which living tissue shows minimum absorption. This has led to crucial applications in medical diagnostics and therapy ("theranostics"), especially with Au nanoshells, nanorods, hollow nanospheres, and nanocubes. In addition, Au nanowires (AuNWs) can be synthesized with longitudinal dimensions of several tens of micrometers and can serve as plasmon waveguides for sophisticated optical devices. The application of anisotropic AuNPs has rapidly spread to optical, biomedical, and catalytic areas. In this Review, a brief historical survey is given, followed by a summary of the synthetic modes, variety of shapes, applications, and toxicity issues of this fast-growing class of nanomaterials. PMID:24421264

  3. Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

    PubMed Central

    Zhang, Xi-Feng; Liu, Zhi-Guo; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. PMID:27649147

  4. Polyphenol-chitosan conjugates: Synthesis, characterization, and applications.

    PubMed

    Hu, Qiaobin; Luo, Yangchao

    2016-10-20

    Chitosan, the only positively charged polysaccharide in the world, is very attractive for food, medicinal and pharmaceutical applications because of its promising properties, including non-toxicity, superb biodegradability, high biocompatibility, abundant availability and low cost. In order to overcome the poor water solubility and widen the applications of chitosan, various polyphenol-chitosan conjugates have been synthesized in recent years. The present review focuses on the chitosan-based conjugates formed using different polyphenols, including gallic acid, caffeic acid, ferulic acid, salicylic acid, catechin, and EGGE, etc. Three major synthesis techniques, namely, activated ester-mediated modification, enzyme-mediated strategy, and free radical induced grafting approach are introduced in detail. In addition, the new physicochemical and biological properties of polyphenol-chitosan conjugates are introduced, including water solubility, thermo stability, in vitro and in vivo antioxidant activity, antimicrobial and anticancer activity. Furthermore, the novel applications of each conjugate are discussed in detail. Lastly, the challenges and prospective areas of study related to polyphenol-chitosan are summarized.

  5. Polyphenol-chitosan conjugates: Synthesis, characterization, and applications.

    PubMed

    Hu, Qiaobin; Luo, Yangchao

    2016-10-20

    Chitosan, the only positively charged polysaccharide in the world, is very attractive for food, medicinal and pharmaceutical applications because of its promising properties, including non-toxicity, superb biodegradability, high biocompatibility, abundant availability and low cost. In order to overcome the poor water solubility and widen the applications of chitosan, various polyphenol-chitosan conjugates have been synthesized in recent years. The present review focuses on the chitosan-based conjugates formed using different polyphenols, including gallic acid, caffeic acid, ferulic acid, salicylic acid, catechin, and EGGE, etc. Three major synthesis techniques, namely, activated ester-mediated modification, enzyme-mediated strategy, and free radical induced grafting approach are introduced in detail. In addition, the new physicochemical and biological properties of polyphenol-chitosan conjugates are introduced, including water solubility, thermo stability, in vitro and in vivo antioxidant activity, antimicrobial and anticancer activity. Furthermore, the novel applications of each conjugate are discussed in detail. Lastly, the challenges and prospective areas of study related to polyphenol-chitosan are summarized. PMID:27474608

  6. Synthesis, characterization, applications, and challenges of iron oxide nanoparticles.

    PubMed

    Ali, Attarad; Zafar, Hira; Zia, Muhammad; Ul Haq, Ihsan; Phull, Abdul Rehman; Ali, Joham Sarfraz; Hussain, Altaf

    2016-01-01

    Recently, iron oxide nanoparticles (NPs) have attracted much consideration due to their unique properties, such as superparamagnetism, surface-to-volume ratio, greater surface area, and easy separation methodology. Various physical, chemical, and biological methods have been adopted to synthesize magnetic NPs with suitable surface chemistry. This review summarizes the methods for the preparation of iron oxide NPs, size and morphology control, and magnetic properties with recent bioengineering, commercial, and industrial applications. Iron oxides exhibit great potential in the fields of life sciences such as biomedicine, agriculture, and environment. Nontoxic conduct and biocompatible applications of magnetic NPs can be enriched further by special surface coating with organic or inorganic molecules, including surfactants, drugs, proteins, starches, enzymes, antibodies, nucleotides, nonionic detergents, and polyelectrolytes. Magnetic NPs can also be directed to an organ, tissue, or tumor using an external magnetic field for hyperthermic treatment of patients. Keeping in mind the current interest in iron NPs, this review is designed to report recent information from synthesis to characterization, and applications of iron NPs. PMID:27578966

  7. Synthesis, characterization, applications, and challenges of iron oxide nanoparticles

    PubMed Central

    Ali, Attarad; Zafar, Hira; Zia, Muhammad; ul Haq, Ihsan; Phull, Abdul Rehman; Ali, Joham Sarfraz; Hussain, Altaf

    2016-01-01

    Recently, iron oxide nanoparticles (NPs) have attracted much consideration due to their unique properties, such as superparamagnetism, surface-to-volume ratio, greater surface area, and easy separation methodology. Various physical, chemical, and biological methods have been adopted to synthesize magnetic NPs with suitable surface chemistry. This review summarizes the methods for the preparation of iron oxide NPs, size and morphology control, and magnetic properties with recent bioengineering, commercial, and industrial applications. Iron oxides exhibit great potential in the fields of life sciences such as biomedicine, agriculture, and environment. Nontoxic conduct and biocompatible applications of magnetic NPs can be enriched further by special surface coating with organic or inorganic molecules, including surfactants, drugs, proteins, starches, enzymes, antibodies, nucleotides, nonionic detergents, and polyelectrolytes. Magnetic NPs can also be directed to an organ, tissue, or tumor using an external magnetic field for hyperthermic treatment of patients. Keeping in mind the current interest in iron NPs, this review is designed to report recent information from synthesis to characterization, and applications of iron NPs. PMID:27578966

  8. Synthesis and application of dipeptides; current status and perspectives.

    PubMed

    Yagasaki, Makoto; Hashimoto, Shin-ichi

    2008-11-01

    The functions and applications of L-alpha-dipeptides (dipeptides) have been poorly studied compared with proteins or amino acids. Only a few dipeptides, such as aspartame (L-aspartyl-L-phenylalanine methyl ester) and L-alanyl-L-glutamine (Ala-Gln), are commercially used. This can be attributed to the lack of an efficient process for dipeptide production though various chemical or chemoenzymatic method have been reported. Recently, however, novel methods have arisen for dipeptide synthesis including a nonribosomal peptide-synthetase-based method and an L-amino acid alpha-ligase-based method, both of which enable dipeptides to be produced through fermentative processes. Since it has been revealed that some dipeptides have unique physiological functions, the progress in production methods will undoubtedly accelerate the applications of dipeptides in many fields. In this review, the functions and applications of dipeptides, mainly in commercial use, and methods for dipeptide production including already proven processes as well as newly developed ones are summarized. As aspartame and Ala-Gln are produced using different industrial processes, the manufacturing processes of these two dipeptides are compared to clarify the characteristics of each procedure.

  9. Altering the Enantioselectivity of Tyrosyl-tRNA Synthetase by Insertion of a Stereospecific Editing Domain.

    PubMed

    Richardson, Charles J; First, Eric A

    2016-03-15

    Translation of mRNAs by the ribosome is stereospecific, with only l-amino acids being incorporated into the nascent polypeptide chain. This stereospecificity results from the exclusion of d-amino acids at three steps during protein synthesis: (1) the aminoacylation of tRNA by aminoacyl-tRNA synthetases, (2) binding of aminoacyl-tRNAs to EF-Tu, and (3) recognition of aminoacyl-tRNAs by the ribosome. As a first step toward incorporating d-amino acids during protein synthesis, we have altered the enantioselectivity of tyrosyl-tRNA synthetase. This enzyme is unusual among aminoacyl-tRNA synthetases, as it can aminoacylate tRNA with d-tyrosine (albeit at a reduced rate compared to l-tyrosine). To change the enantioselectivity of tyrosyl-tRNA synthetase, we introduced the post-transfer editing domain from Pyrococcus horikoshii phenylalanyl-tRNA synthetase into the connective polypeptide 1 (CP1) domain of Geobacillus stearothermophilus tyrosyl-tRNA synthetase (henceforth designated TyrRS-FRSed). We show that the phenylalanyl-tRNA synthetase editing domain is stereospecific, hydrolyzing l-Tyr-tRNA(Tyr), but not d-Tyr-tRNA(Tyr). We further show that inserting the phenylalanyl-tRNA synthetase editing domain into the CP1 domain of tyrosyl-tRNA synthetase decreases the activity of the synthetic site in tyrosyl-tRNA synthetase. This decrease in activity is critical, as it prevents the rate of synthesis from overwhelming the ability of the editing domain to hydrolyze the l-Tyr-tRNA(Tyr) product. Overall, inserting the phenylalanyl-tRNA synthetase editing domain results in a 2-fold shift in the enantioselectivity of tyrosyl-tRNA synthetase toward the d-Tyr-tRNA(Tyr) product. When a 4-fold excess of d-tyrosine is used, approximately 40% of the tRNA(Tyr) is aminoacylated with d-tyrosine. PMID:26890980

  10. Development of a Double Allylboration Reagent Targeting 1,5-syn-(E)-Diols: Application to the Synthesis of the C(23)-C(40) Fragment of Tetrafibricin

    PubMed Central

    Nuhant, Philippe; Kister, Jeremy; Lira, Ricardo; Sorg, Achim; Roush, William R.

    2011-01-01

    Interest in the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin prompted us to develop a new method for the synthesis of 1,5-syn-(E)-diols. Toward this end, the kinetically controlled hydroboration of allenes 6, 33, ent-39, 42 and 45 with the Soderquist borane 25R were studied. Tetrabutylammonium allenyltrifluoroborate 45 gave superior results and was utilized in a double allylboration sequence with two different aldehydes to provide the targeted 1,5-syn-(E)-diols in generally high yields (72–98%), and with high enantioselectivity (>95% e.e.), diastereoselectivity (d.r. >20:1), and (E)/(Z) selectivity (>20:1). This new method was applied to the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin. PMID:21857752

  11. Enantioselective palladium-catalyzed C-H functionalization of indoles using an axially chiral 2,2'-bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Huang, Wen-Xue; Chen, Mu-Wang; Zhou, Yong-Gui

    2015-10-01

    A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.

  12. Synthesis of Chiral Cyclopentenones.

    PubMed

    Simeonov, Svilen P; Nunes, João P M; Guerra, Krassimira; Kurteva, Vanya B; Afonso, Carlos A M

    2016-05-25

    The cyclopentenone unit is a very powerful synthon for the synthesis of a variety of bioactive target molecules. This is due to the broad diversity of chemical modifications available for the enone structural motif. In particular, chiral cyclopentenones are important precursors in the asymmetric synthesis of target chiral molecules. This Review provides an overview of reported methods for enantioselective and asymmetric syntheses of cyclopentenones, including chemical and enzymatic resolution, asymmetric synthesis via Pauson-Khand reaction, Nazarov cyclization and organocatalyzed reactions, asymmetric functionalization of the existing cyclopentenone unit, and functionalization of chiral building blocks. PMID:27101336

  13. Enantioselective esterification of racemic ibuprofen in isooctane by immobilized lipase on cellulose acetate-titanium iso-propoxide gel fiber.

    PubMed

    Ikeda, Yuko; Kurokawa, Youichi

    2002-01-01

    Lipase (Candida rugosa) was entrap-immobilized on cellulose acetate-titanium iso-propoxide gel fiber by the sol-gel method. The immobilized lipase was used for the direct synthesis of (S)-ibuprofen ester from racemic ibuprofen using propyl alcohol as an acyl acceptor in isooctane. The activity of the immobilized lipase was decreased to about 10-20% that of native lipase. However, the reaction was more enantioselective compared to that with native lipase. The stability for repeated use was improved by immobilization.

  14. Triply Hydrogen-Bond-Directed Enantioselective Assembly of Pyrrolobenzo-1,4-diazine Skeletons with Quaternary Stereocenters.

    PubMed

    Shen, Xiaoming; Wang, Yongtao; Wu, Tiandi; Mao, Zhenjun; Lin, Xufeng

    2015-06-15

    Highly efficient synthesis of optically enriched pyrrolobenzo-1,4-diazines bearing quaternary stereocenters has been realized through the chiral Brønsted acid-catalyzed Pictet-Spengler reaction of 2-(1H-pyrrol-1-yl)anilines and α-ketoamides in good to excellent yields and enantioselectivities. Computational studies suggest an unprecedented phenomenon whereby the chiral phosphoric acid catalyst employs attractive arene C-H⋅⋅⋅N hydrogen bonding to activate the substrate and induce chirality through a triple hydrogen-bonding interaction. PMID:25965054

  15. Use of a New Spirophosphine to Achieve Catalytic Enantioselective [4+1] Annulations of Amines with Allenes to Generate Dihydropyrroles

    PubMed Central

    Kramer, Søren; Fu, Gregory C.

    2015-01-01

    Due in part to the common occurrence of five-membered nitrogen heterocycles in bioactive molecules, the discovery of methods for the enantioselective synthesis of such structures is a useful endeavor. Building on a single example by Tong of a phosphine-catalyzed [4+1] annulation of an amine with an allene that furnished an achiral dihydropyrrole in 22% yield, we have developed, with the aid of a new chiral spirophosphine catalyst, a method with increased utility, specifically, improved yield, enhanced scope (the use of γ-substituted allenes), and good ee. The enantioenriched dihydropyrrole products can be transformed into other interesting families of compounds with very good stereoselectivity. PMID:25780940

  16. Enantioselective separations using chiral supported liquid crystalline membranes.

    PubMed

    Han, Sangil; Rabie, Feras; Marand, Eva; Martin, Stephen M

    2012-07-01

    Porous and nonporous supported liquid crystalline membranes were produced by impregnating porous cellulose nitrate supports with cholesteric liquid crystal (LC) materials consisting of 4-cyano-4'-pentylbiphenyl (5CB) mixed with a cholesterol-based dopant (cholesteryl oleyl carbonate [COC], cholesteryl nonanoate [CN], or cholesteryl chloride [CC]). The membranes exhibit selectivity for R-phenylglycine and R-1-phenylethanol because of increased interactions between the S enantiomers and the left-handed cholesteric phase. The selectivity of both phenylglycine and 1-phenylethanol in 5CB/CN membranes decreases with effective pore diameter while the permeabilities increase, as expected. Phenylglycine, which is insoluble in the LC phase, exhibits no transport in the nonporous (completely filled) membranes; however, 1-phenylethanol, which is soluble in the LC phase, exhibits transport but negligible enantioselectivity. The enantioselectivity for 1-phenylethanol was higher (1.20 in 5CB/COC and 5CB/CN membranes) and the permeability was lower in the cholesteric phase than in the isotropic phase. Enantioselectivity was also higher in the 5CB/COC cholesteric phase than in the nematic phase of undoped 5CB (1.03). Enantioselectivity in the cholesteric phase of 5CB doped with CC (1.1), a dopant lacking hydrogen bonding groups, was lower than in the 5CB/COC phases. Finally, enantioselectivity increases with the dopant concentration up to a plateau value at approximately 17 mol%. PMID:22581655

  17. Development of Catalysts and Ligands for Enantioselective Gold Catalysis

    PubMed Central

    Wang, Yi-Ming; Lackner, Aaron D.; Toste, F. Dean

    2014-01-01

    CONSPECTUS The use of Au(I) complexes for the catalytic activation of C-C π-bonds has been the subject of intense investigation in the last decade or so. The facile formation of carbon-carbon and carbon-heteroatom bonds facilitated by gold naturally led to efforts to render these transformations enantioselective. Early examples of enantioselective gold-catalyzed transformations have focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, careful choice of the weakly coordinating ligand (or counterion) was needed to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, a new class of mononuclear phosphite and phosphoramidite ligands was developed to supplement the previously widely utilized phosphines. Finally carbene ligands, in particular, the acyclic diaminocarbenes, have also been successfully applied to enantioselective transformations. PMID:24228794

  18. Diastereoselective Total Synthesis of (-)-Galiellalactone.

    PubMed

    Kim, Taewoo; Han, Young Taek; An, Hongchan; Kim, Kyeojin; Lee, Jeeyeon; Suh, Young-Ger

    2015-12-18

    An enantioselective total synthesis of (-)-galiellalactone has been accomplished. The key features of the synthesis involve the highly stereoselective construction of the cis-trisubstituted cyclopentane intermediate by a Pd(0)-catalyzed cyclization, the stereospecific introduction of an angular hydroxyl group by Riley oxidation, and the efficient construction of the tricyclic system of (-)-galiellalactone via a combination of diastereoselective Hosomi-Sakurai crotylation and ring-closing metathesis (RCM). PMID:26544529

  19. Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis.

    PubMed

    Breipohl, G; Knolle, J; Stüber, W

    1989-10-01

    The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4-dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C-terminal hexapeptide of secretin are given as examples.

  20. Green synthesis and applications of Au-Ag bimetallic nanoparticles

    NASA Astrophysics Data System (ADS)

    Meena Kumari, M.; Jacob, John; Philip, Daizy

    2015-02-01

    This paper reports for the first time the synthesis of bimetallic nanoparticles at room temperature using the fruit juice of pomegranate. Simultaneous reduction of gold and silver ions in different molar ratios leads to the formation of alloy as well as core-shell nanostructures. The nanoparticles have been characterized using UV-vis spectroscopy, transmission electron microscopy, Fourier Transform Infrared Spectroscopy and X-ray diffraction. The synthesized alloy particles are used as catalysts in the reduction of 2-, 3-, 4-nitrophenols to the corresponding amines and in the degradation of methyl orange. The reduction kinetics for all the reactions follows pseudo-first order. The rate constants follow the order k4-nitrophenol < k2-nitrophenol < k3-nitrophenol. Thermal conductivity is measured as a function of volume fraction and it is observed that the incorporation of the alloy nanoparticles enhances the thermal conductivity of the base fluid (water) showing nanofluid application. The nitric oxide and hydroxyl radical scavenging activity shown by the nanoparticles promise the potential application in biomedical field.

  1. Yolk/shell nanoparticles: classifications, synthesis, properties, and applications.

    PubMed

    Purbia, Rahul; Paria, Santanu

    2015-12-21

    Core/shell nanoparticles were first reported in the early 1990s with a simple spherical core and shell structure, but the area is gradually diversifying in multiple directions such as different shapes, multishells, yolk/shell etc., because of the development of different new properties of the materials, which are useful for several advanced applications. Among different sub-areas of core/shell nanoparticles, yolk/shell nanoparticles (YS NPs) have drawn significant attention in recent years because of their unique properties such as low density, large surface area, ease of interior core functionalization, a good molecular loading capacity in the void space, tunable interstitial void space, and a hollow outer shell. The YS NPs have better properties over simple core/shell or hollow NPs in various fields including biomedical, catalysis, sensors, lithium batteries, adsorbents, DSSCs, microwave absorbers etc., mainly because of the presence of free void space, porous hollow shell, and free core surface. This review presents an extensive classification of YS NPs based on their structures and types of materials, along with synthesis strategies, properties, and applications with which one would be able to draw a complete picture of this area.

  2. Green synthesis and applications of Au-Ag bimetallic nanoparticles.

    PubMed

    Meena Kumari, M; Jacob, John; Philip, Daizy

    2015-02-25

    This paper reports for the first time the synthesis of bimetallic nanoparticles at room temperature using the fruit juice of pomegranate. Simultaneous reduction of gold and silver ions in different molar ratios leads to the formation of alloy as well as core-shell nanostructures. The nanoparticles have been characterized using UV-vis spectroscopy, transmission electron microscopy, Fourier Transform Infrared Spectroscopy and X-ray diffraction. The synthesized alloy particles are used as catalysts in the reduction of 2-, 3-, 4-nitrophenols to the corresponding amines and in the degradation of methyl orange. The reduction kinetics for all the reactions follows pseudo-first order. The rate constants follow the order k4-nitrophenolapplication. The nitric oxide and hydroxyl radical scavenging activity shown by the nanoparticles promise the potential application in biomedical field. PMID:25218228

  3. Silatranes: a review on their synthesis, structure, reactivity and applications.

    PubMed

    Puri, J K; Singh, Raghubir; Chahal, Varinder Kaur

    2011-03-01

    This critical review summarizes progress of the rapidly developing and very active field of silatrane chemistry. The first part of the review deals with general synthetic approaches used to synthesize different silatranes. The most interesting feature of silatranes, i.e., variation of Si-N bond length on the basis of the axial substituent of Si, and other structural features, are described in the second part with special emphasis on crystallographic and theoretical studies. It is followed by a discussion on the reactivity of various silatranes. Silatranes have now gained acceptance for a wide variety of applications which are summarized in the last section of review. Some of them have extensive interest due to their medical use to heal wounds or stimulate hair-growth (pilotropic activity), biological properties, pharmacological properties e.g. antitumor, anticancer, antibacterial, anti-inflammatory, fungicidal activity, stimulating effect in animal production and seed germination effects. The review focuses on the extended potential of silatranes in sol-gel processes, mesoporous zeotypes, atomic force microscopy, commercial products such as adhesion promoters, polymer formation and rubber compositions. This critical review will be helpful for general researchers, experts, advanced undergraduates and newcomers working on silatrane chemistry as this review presents greater emphasis on synthesis and characterization, structural properties, reactivity and applications of silatranes in the field of biology, material science, sol-gel chemistry, pharmaceutics, agriculture and medicine (311 references).

  4. Nanostructured organic electronic materials: Synthesis and sensor applications

    NASA Astrophysics Data System (ADS)

    Dua, Vineet

    2009-12-01

    This study is an investigation into (a) the process by which one obtains bulk quantities of nanofibers of parent polythiophene, (b) in-situ deposition of nanofibers of polythiophene on flexible substrate and its application in vapor sensing, and (c) inkjet printing of graphene on flexible substrate and its application as a detector. (a) The 2 nd chapter of the thesis is an extension of "seeding" method from aqueous to organic solvents to synthesize parent polythiophene nanofibers. Bulk quantities of parent polythiophene nanofibers were synthesized in one step using catalytic amounts of freeze dried V2O5. This work is published in Chemistry Letters 2008 37(5), 526--527. (b) The 3rd chapter deals with in-situ films of polythiophene nanofibers on plastic substrates. In this a one step method to directly deposit nanofibers of parent polythiophene on flexible substrate is discussed. These films show a reversible detection of highly oxidizing vapors such as NO2, Cl2 and SO 2 at ppb levels under ambient conditions. This work is published in Macromolecules 2009, 42, 5414--5415. (c) The 4 th chapter describes the synthesis of reduced graphene oxide (RGO) using a mild reducing agent ascorbic acid (Vitamin C) rather than traditionally used harsh reducing agents (N2H4). Dispersions of RGO were inkjet printed on flexible substrate and has been shown to detect aggressive vapors NO2 and Cl2 at ambient conditions. This work is accepted for publication in Angewandte Chemie (Nov 2009).

  5. Synthesis and Characterization of Photosensitive Polyimides for Optical Applications

    NASA Astrophysics Data System (ADS)

    Kim, Kye-Hyun

    1995-11-01

    The objective of this research was to prepare photosensitive polyimides for optical applications. The work was begun with the synthesis of a series of poly(amic esters) containing cinnamyl groups. However, these systems required high imidization temperatures where they darkened considerably. Two new photosensitive end-capping agents, i.e., 6-(4-aminophenoxy)hexyl methacrylate, and di(2-(methacryloyloxy)ethyl) 5-aminoisophthalate, for polyimides were also prepared. These agents were used along with 2,2^' -bis(3,4-dicarboxyphenyl)hexafluoropropane dianhydride (6FDA) and 2,2^'-bis(trifluoromethyl) -4,4^' -diaminobiphenyl (PFMB) to prepare a series of methacrylate end-capped imide oligomers. However, the oligomers required long exposures to UV-radiation to affect cure. To improve their photosensitivity, multifunctional additives and photoinitiators were used. A difunctional end-capped oligomer that contained trimethylolpropane triacrylate (TMPTA) and trimethylbenzoyldiphenyl phosphine oxide (TMDPO) was highly photosensitive and displayed good photo-patterning properties. The third approach involved the synthesis of a diamine monomer in which methacrylate moieties were attached to the 2- and 2^ '-positions of biphenyl structures. The monomer, i.e., 2,2^'-dimethacryloyloxy -4,4^'-diaminobiphenyl (DMB), was polymerized with commercially available dianhydrides such as 6FDA and 4,4^' -oxydiphthalic anhydride (ODPA). The polyimides obtained were optically transparent and soluble in common organic solvents such as acetone and chloroform. The polymers were highly photosensitive and displayed good photo-patterning properties. The polymers, which afforded high-resolution patterns, did not develop color or shrink during UV-exposure and thermal curing.

  6. 77 FR 8324 - Applications for the Environment: Real-Time Information Synthesis (AERIS) User Needs Workshop...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-14

    ... Applications for the Environment: Real-Time Information Synthesis (AERIS) User Needs Workshop; Notice of Public...: Real- Time Information Synthesis (AERIS) Program and solicit user needs for its Transformative Concepts... program is to generate and acquire environmentally-relevant real-time transportation data, and use...

  7. Immobilization and characterization of a new regioselective and enantioselective lipase obtained from a metagenomic library.

    PubMed

    Alnoch, Robson Carlos; Martini, Viviane Paula; Glogauer, Arnaldo; Costa, Allen Carolina dos Santos; Piovan, Leandro; Muller-Santos, Marcelo; de Souza, Emanuel Maltempi; de Oliveira Pedrosa, Fábio; Mitchell, David Alexander; Krieger, Nadia

    2015-01-01

    In previous work, a new lipase and its cognate foldase were identified and isolated from a metagenomic library constructed from soil samples contaminated with fat. This new lipase, called LipG9, is a true lipase that shows specific activities that are comparable to those of well-known industrially-used lipases with high activity against long-chain triglycerides. In the present work, LipG9 was co-expressed and co-immobilized with its foldase, on an inert hydrophobic support (Accurel MP1000). We studied the performance of this immobilized LipG9 (Im-LipG9) in organic media, in order to evaluate its potential for use in biocatalysis. Im-LipG9 showed good stability, maintaining a residual activity of more than 70% at 50 °C after incubation in n-heptane (log P 4.0) for 8 h. It was also stable in polar organic solvents such as ethanol (log P -0.23) and acetone (log P -0.31), maintaining more than 80% of its original activity after 8 h incubation at 30 °C. The synthesis of ethyl esters was tested with fatty acids of different chain lengths in n-heptane at 30 °C. The best conversions (90% in 3 h) were obtained for medium and long chain saturated fatty acids (C8, C14 and C16), with the maximum specific activity, 29 U per gram of immobilized preparation, being obtained with palmitic acid (C16). Im-LipG9 was sn-1,3-specific. In the transesterification of the alcohol (R,S)-1-phenylethanol with vinyl acetate and the hydrolysis of the analogous ester, (R,S)-1-phenylethyl acetate, Im-LipG9 showed excellent enantioselectivity for the R-isomer of both substrates (E> 200), giving an enantiomeric excess (ee) of higher than 95% for the products at 49% conversion. The results obtained in this work provide the basis for the development of applications of LipG9 in biocatalysis. PMID:25706996

  8. Immobilization and Characterization of a New Regioselective and Enantioselective Lipase Obtained from a Metagenomic Library

    PubMed Central

    Alnoch, Robson Carlos; Martini, Viviane Paula; Glogauer, Arnaldo; Costa, Allen Carolina dos Santos; Piovan, Leandro; Muller-Santos, Marcelo; de Souza, Emanuel Maltempi; de Oliveira Pedrosa, Fábio; Mitchell, David Alexander; Krieger, Nadia

    2015-01-01

    In previous work, a new lipase and its cognate foldase were identified and isolated from a metagenomic library constructed from soil samples contaminated with fat. This new lipase, called LipG9, is a true lipase that shows specific activities that are comparable to those of well-known industrially-used lipases with high activity against long-chain triglycerides. In the present work, LipG9 was co-expressed and co-immobilized with its foldase, on an inert hydrophobic support (Accurel MP1000). We studied the performance of this immobilized LipG9 (Im-LipG9) in organic media, in order to evaluate its potential for use in biocatalysis. Im-LipG9 showed good stability, maintaining a residual activity of more than 70% at 50°C after incubation in n-heptane (log P 4.0) for 8 h. It was also stable in polar organic solvents such as ethanol (log P -0.23) and acetone (log P -0.31), maintaining more than 80% of its original activity after 8 h incubation at 30°C. The synthesis of ethyl esters was tested with fatty acids of different chain lengths in n-heptane at 30 °C. The best conversions (90% in 3 h) were obtained for medium and long chain saturated fatty acids (C8, C14 and C16), with the maximum specific activity, 29 U per gram of immobilized preparation, being obtained with palmitic acid (C16). Im-LipG9 was sn-1,3-specific. In the transesterification of the alcohol (R,S)-1-phenylethanol with vinyl acetate and the hydrolysis of the analogous ester, (R,S)-1-phenylethyl acetate, Im-LipG9 showed excellent enantioselectivity for the R-isomer of both substrates (E> 200), giving an enantiomeric excess (ee) of higher than 95% for the products at 49% conversion. The results obtained in this work provide the basis for the development of applications of LipG9 in biocatalysis. PMID:25706996

  9. Sustainable synthesis, characterization, and applications of metal oxide nanostructures

    NASA Astrophysics Data System (ADS)

    Tiano, Amanda Lyn

    Nanomaterials have attracted significant research focus due to their advantageous and unique properties (i.e. electronic, magnetic, optical, and mechanical) as compared with the bulk. Metal oxide nanostructures are of particular interest, as they are very robust and display high chemical and thermal stability, while offering a diverse array of fascinating properties. By reliably controlling the size, morphology, composition, and crystallinity of these nanostructures, their properties can be tuned for a specific purpose. These advantageous tailorable properties render them as ideal candidates for many applications such as catalysis, sensing, electronics, optoelectronics, energy storage, and even medicine. Driven by their increased popularity and potential applications, efforts to synthesize nanomaterials have moved toward environmentally-friendly methodologies, such as wet-chemical, molten-salt, hydrothermal, and sol-gel methods. We will discuss the green synthesis of strontium ruthenate (SrRuO 3), the yttrium manganese oxides (YMnO3 and YMn2O 5), and the magnetic spinel ferrites (MFe2O4 where 'M' is Mg, Fe, Co, Ni, Cu, and Zn) and our ability to reliably tune their properties for various applications. The effects of the molten salt parameters on the resulting particle size and morphology were explored for SrRuO 3 and the yttrium manganese oxides. For example, rapid cooling rates and the use of surfactants allowed us to produced faceted octahedra of SrRuO 3, which resulted in a 4-fold enhancement of their activity towards methanol oxidation with respect to smooth rounded particles. Similarly, using the hydrothermal method, we generated ferrite nanoparticles of different compositions and sizes. We investigated their potential as contrast agents for magnetic resonance imaging (MRI) and as photocatalysts, and observed significant differences as a function of both size and composition. Similarly, we will also examine surface and structural effects upon the electronic

  10. Synthesis, characterization and biosensing application of photon upconverting nanoparticles

    NASA Astrophysics Data System (ADS)

    Kumar, Manoj; Zhang, Peng

    2009-02-01

    Phosphor/fluorescent molecules/particles have been widely used in various applications for quite some time. Typically, light with longer wavelength(s) is emitted when excited by shorter wavelength light. The opposite effect also exists, where a phosphor particle is excited with an infrared or red light and emits color(s) of shorter wavelengths, a process called up-conversion. Materials with upconverting properties have narrower absorption and line emission spectra than their down-converting counterparts. Because most non-target materials in a complex mixture do not possess such photon up-conversion properties, a dramatically improved S/N ratio is expected in sensing and luminescence reporting applications. This makes photon upconverting materials ideal for identification of trace amounts of target molecules. Here we report the synthesis, characterization and DNA detection application based on NaYF4:Yb3+, Er3+ photon upconverting nanoparticles. The design of a nucleotide sensor for the detection of point mutation associated with sickle cell disease is described. The underlying principle for the detection is luminescence resonance energy transfer (LRET), with the photon upconverting nanoparticle as the donor and a dye, N,N,N',N'-tetramethyl-6-carboxyrhodamine (TAMRA), as the acceptor. The detection scheme is based on a sandwich-type hybridization format. The presence of the target DNA is indicated by the increase of the normalized acceptor's emission. Based on photon upconverting nanoparticles, which display high S/N ratio and no photobleaching, the DNA sensor demonstrates high sensitivity and specificity. The results demonstrate great potential of such nanomaterials as oligonucleotide sensors.

  11. Colloidal-sized metal-organic frameworks: synthesis and applications.

    PubMed

    Sindoro, Melinda; Yanai, Nobuhiro; Jee, Ah-Young; Granick, Steve

    2014-02-18

    Colloidal metal-organic frameworks (CMOFs), nanoporous colloidal-sized crystals that are uniform in both size and polyhedral shape, are crystals composed of metal ions and organic bridging ligands, which can be used as building blocks for self-assembly in organic and aqueous liquids. They stand in contrast to conventional metal-organic frameworks (MOFs), which scientists normally study in the form of bulk crystalline powders. However, powder MOFs generally have random crystal size and shape and therefore do not possess either a definite mutual arrangement with adjacent particles or uniformity. CMOFs do have this quality, which can be important in vital uptake and release kinetics. In this Account, we present the diverse methods of synthesis, pore chemistry control, surface modification, and assembly techniques of CMOFs. In addition, we survey recent achievements and future applications in this emerging field. There is potential for a paradigm shift, away from using just bulk crystalline powders, towards using particles whose size and shape are regulated. The concept of colloidal MOFs takes into account that nanoporous MOFs, conventionally prepared in the form of bulk crystalline powders with random crystal size, shape, and orientation, may also form colloidal-sized objects with uniform size and morphology. Furthermore, the traditional MOF functions that depend on porosity present additional control over those MOF functions that depend on pore interactions. They also can enable controlled spatial arrangements between neighboring particles. To begin, we discuss progress regarding synthesis of MOF nano- and microcrystals whose crystal size and shape are well regulated. Next, we review the methods to modify the surfaces with dye molecules and polymers. Dyes are useful when seeking to observe nonluminescent CMOFs in situ by optical microscopy, while polymers are useful to tune their interparticle interactions. Third, we discuss criteria to assess the stability of CMOFs

  12. Colloidal-sized metal-organic frameworks: synthesis and applications.

    PubMed

    Sindoro, Melinda; Yanai, Nobuhiro; Jee, Ah-Young; Granick, Steve

    2014-02-18

    Colloidal metal-organic frameworks (CMOFs), nanoporous colloidal-sized crystals that are uniform in both size and polyhedral shape, are crystals composed of metal ions and organic bridging ligands, which can be used as building blocks for self-assembly in organic and aqueous liquids. They stand in contrast to conventional metal-organic frameworks (MOFs), which scientists normally study in the form of bulk crystalline powders. However, powder MOFs generally have random crystal size and shape and therefore do not possess either a definite mutual arrangement with adjacent particles or uniformity. CMOFs do have this quality, which can be important in vital uptake and release kinetics. In this Account, we present the diverse methods of synthesis, pore chemistry control, surface modification, and assembly techniques of CMOFs. In addition, we survey recent achievements and future applications in this emerging field. There is potential for a paradigm shift, away from using just bulk crystalline powders, towards using particles whose size and shape are regulated. The concept of colloidal MOFs takes into account that nanoporous MOFs, conventionally prepared in the form of bulk crystalline powders with random crystal size, shape, and orientation, may also form colloidal-sized objects with uniform size and morphology. Furthermore, the traditional MOF functions that depend on porosity present additional control over those MOF functions that depend on pore interactions. They also can enable controlled spatial arrangements between neighboring particles. To begin, we discuss progress regarding synthesis of MOF nano- and microcrystals whose crystal size and shape are well regulated. Next, we review the methods to modify the surfaces with dye molecules and polymers. Dyes are useful when seeking to observe nonluminescent CMOFs in situ by optical microscopy, while polymers are useful to tune their interparticle interactions. Third, we discuss criteria to assess the stability of CMOFs

  13. Synthesis and Applications of Inorganic/Organic-Polymer Nanocomposites

    NASA Astrophysics Data System (ADS)

    Goyal, Anubha

    This research work focuses on developing new synthesis routes to fabricate polymer nanocomposites tailored towards different applications. A simple, one-step method has been devised for synthesizing free-standing, flexible metal nanoparticle-polydimethylsiloxane films. This process simplifies prevalent methods to synthesize nanocomposites, in that here nanoparticles are created in situ while curing the polymer. This route circumvents the need for pre-synthesized nanoparticles, external reducing agents and stabilizers, thereby significantly reducing processing time and cost. The resulting nanocomposite also demonstrates enhancement in mechanical and antibacterial properties, with other envisaged applications in biomedical devices and catalysis. Applying the same mechanism as that used for the formation of bulk metalsiloxane nanocomposites, metal core-siloxane shell nanoparticles and siloxane nanowires were synthesized, with octadecylsilane as the precursor and in situ formed metal nanoparticles (gold, silver) as the catalyst. This method offers some unique advantages over the previously existing methods. This is a room temperature route which does not require high temperature refluxing or the use of pre-synthesized nanoparticles. Furthermore, this synthesis process gives a control over the shape of resulting nanocomposite structures (1-D wires or 0-D spherical particles). High thermal stability of polydimethylsiloxane (PDMS) makes it viable to alternatively synthesize metal nanoparticles in the polymer matrix by thermal decomposition process. This technique is generic across a range of metals (palladium, iron, nickel) and results in nanoparticles with a very narrow size distribution. Membranes with palladium nanoparticles demonstrate catalytic activity in ethylene hydrogenation reaction. Additionally, a new nanocomposite electrode has been developed for flexible and light-weight Li-ion batteries. Flexible films were prepared by the integration of the poly

  14. Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones

    PubMed Central

    Kwiatkowski, Piotr; Beeson, Teresa D.; Conrad, Jay C.

    2011-01-01

    The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio- and chemoselective catalyst control in fluorinations involving complex carbonyl systems. PMID:21247133

  15. Enantioselective Iodolactonization of Disubstituted Olefinic Acids Using a Bifunctional Catalyst

    PubMed Central

    Fang, Chao; Paull, Daniel H.; Hethcox, J. Caleb; Shugrue, Christopher R.; Martin, Stephen F.

    2012-01-01

    The enantioselective iodolactonizations of a series of diversely-substituted olefinic carboxylic acids are promoted by a BINOL-derived, bifunctional catalyst. Reactions involving 5-alkyl- and 5-aryl-4(Z)-pentenoic acids and 6-alkyl- and 6-aryl-5(Z)-hexenoic acids provide the corresponding γ- and δ-lactones having stereogenic C–I bonds in excellent yields and >97:3 er. Significantly, this represents the first organocatalyst that promotes both bromo- and iodolactonization with high enantioselectivities. The potential of this catalyst to induce kinetic resolutions of racemic unsaturated acids is also demonstrated. PMID:23199100

  16. Enantioselective synthesis of L-(-)-4- boronophenylalanine (L-BPA)

    DOEpatents

    Samsel, Edward G.

    1992-01-01

    A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4-bromobenzaldehyde with ethylene glycol to form 4-bromobenzaldehyde ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-.alpha.-benzoylamino-4-boronocinnamic acid, asymmetrically hydrogenating the z-.alpha.-benzoylamino-4-boronocinnamic acid in the presence of a catalyst of a cheltate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA.

  17. Enantioselective synthesis of L-(-)-4- boronophenylalanine (L-BPA)

    DOEpatents

    Samsel, E.G.

    1992-10-20

    A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4-bromobenzaldehyde with ethylene glycol to form 4-bromobenzaldehyde ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-[alpha]-benzoylamino-4boronocinnamic acid, asymmetrically hydrogenating the z-[alpha]-benzoylamino-4-boronocinnamic acid in the presence of a catalyst of a cheltate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA. 3 figs.

  18. Sulfoxide-directed enantioselective synthesis of functionalized tetrahydropyridines.

    PubMed

    Fernández de la Pradilla, Roberto; Simal, Carmen; Bates, Robert H; Viso, Alma; Infantes, Lourdes

    2013-10-01

    The highly selective base-promoted cyclization of enantiopure sulfinyl dienamines provides stereodefined sulfinyl 1,2,3,6-tetrahydropyridines (dr up to 99:1). Subsequent sigmatropic rearrangement affords tetrahydropyridin-3-ols in good yields and selectivities.

  19. Highly enantioselective synthesis of isoxazoline N-oxides.

    PubMed

    Zhu, Chun-Yin; Deng, Xian-Ming; Sun, Xiu-Li; Zheng, Jun-Cheng; Tang, Yong

    2008-02-14

    The reaction of cinchonidine (cinchonine)-derived ammonium salts with nitroolefins in the presence of Cs2CO3 to afford optically active isoxazoline N-oxides with excellent ee and high de values has been developed.

  20. Synthetic applications of pseudocyclic hypervalent iodine compounds.

    PubMed

    Yoshimura, Akira; Yusubov, Mekhman S; Zhdankin, Viktor V

    2016-06-01

    Hypervalent iodine compounds have found wide practical application as versatile, efficient, and sustainable reagents for organic synthesis. Pseudocyclic hypervalent iodine derivatives are characterized by the presence of additional intramolecular non-covalent coordination at the iodine center, which leads to significant alteration of their physical and chemical properties. In comparison with common hypervalent iodine reagents, these pseudocyclic compounds have higher thermal stability, better solubility, and improved reactivity. In recent years, pseudocyclic hypervalent iodine reagents are increasingly used in organic synthesis as environmentally friendly selective oxidants and electrophiles. Furthermore, numerous enantioselective reactions mediated by chiral pseudocyclic hypervalent iodine species have been recently developed. In the present review, the preparation and structural features of pseudocyclic iodine(iii) and iodine(v) derivatives are discussed, and recent developments in their synthetic applications are summarized. PMID:27143521

  1. Sonochemical synthesis of manganese (II) hydroxide for supercapacitor applications

    SciTech Connect

    Anandan, Sambandam; Gnana Sundara Raj, Balasubramaniam; Lee, Gang-Juan; Wu, Jerry J.

    2013-09-01

    Graphical abstract: - Highlights: • Octahedral Mn(OH){sub 2} nanoparticles were prepared by sonochemical process. • TEM images indicates the formation of octahedral Mn(OH){sub 2} nanoparticles. • Octahedral Mn(OH){sub 2} nanoparticles are evaluated as a supercapacitor material. - Abstract: In this research, a rapid and controllable synthesis of octahedral Mn(OH){sub 2} nanoparticles with a size range from 140 to 200 nm has been done by a sonochemial irradiation method for the energy storage applications. Transmission electron microscopic images, energy disperse X-ray spectroscopy (EDX), X-ray photo electron spectroscopy (XPS), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) analyses clearly indicate the formation of octahedral Mn(OH){sub 2} nanoparticles. Octahedral Mn(OH){sub 2} nanoparticles were evaluated as a supercapacitor material that exhibits specific capacitance 127 F g{sup −1} at a current density of 0.5 mA cm{sup −2} in the potential range from −0.1 to 0.8 V in 1 M Na{sub 2}SO{sub 4} solution.

  2. Silver nanoparticles: synthesis, properties, toxicology, applications and perspectives

    NASA Astrophysics Data System (ADS)

    Tran, Quang Huy; Quy Nguyen, Van; Le, Anh-Tuan

    2013-09-01

    In recent years the outbreak of re-emerging and emerging infectious diseases has been a significant burden on global economies and public health. The growth of population and urbanization along with poor water supply and environmental hygiene are the main reasons for the increase in outbreak of infectious pathogens. Transmission of infectious pathogens to the community has caused outbreaks of diseases such as influenza (A/H5N1), diarrhea (Escherichia coli), cholera (Vibrio cholera), etc throughout the world. The comprehensive treatments of environments containing infectious pathogens using advanced disinfectant nanomaterials have been proposed for prevention of the outbreaks. Among these nanomaterials, silver nanoparticles (Ag-NPs) with unique properties of high antimicrobial activity have attracted much interest from scientists and technologists to develop nanosilver-based disinfectant products. This article aims to review the synthesis routes and antimicrobial effects of Ag-NPs against various pathogens including bacteria, fungi and virus. Toxicology considerations of Ag-NPs to humans and ecology are discussed in detail. Some current applications of Ag-NPs in water-, air- and surface- disinfection are described. Finally, future prospects of Ag-NPs for treatment and prevention of currently emerging infections are discussed.

  3. Surfactantless synthesis of silver nanoplates and their application in SERS.

    SciTech Connect

    Sun, Y.; Wiederrecht, G.; Center for Nanoscale Materials

    2007-11-01

    Silver nanoplates with thicknesses of 50-70 nm and edge lengths ranging from 200 nm to 1 mm are grown on semiconductor waters at room temperature through a simple galvanic reaction between an aqueous solution of silver nitrate and n-type GaAs. The as-grown silver structures have chemically clean surfaces because no surfactant or coordinating molecules are involved in the synthesis. Electron microscopy characterization indicates that each silver plate has rough surfaces and a half-moon morphology with one straight edge and on arclike edge. Systematic studies on varying reaction conditions reveal that the oxide (i.e., Ga{sub 2}O{sub 3} and As{sub 2}O{sub 3}) layers of GaAs, generated in situ in the reactions, play an important role in assisting the growth of anisotropic nanoplates. The cleanliness of the surfaces of the silver nanoplates is beneficial to attachment of interesting molecules on their surfaces for various applications, such as plasmonic-enhanced photophysical and photochemical processes and surface-enhanced spectroscopies.

  4. Zinc impregnated cellulose nanocomposites: Synthesis, characterization and applications

    NASA Astrophysics Data System (ADS)

    Ali, Attarad; Ambreen, Sidra; Maqbool, Qaisar; Naz, Sania; Shams, Muhammad Fahad; Ahmad, Madiha; Phull, Abdul Rehman; Zia, Muhammad

    2016-11-01

    Nanocomposite materials have broad applicability due to synergistic effect of combined components. In present investigation, cellulose isolated from citrus peel waste is used as a supporting material; impregnation of zinc oxide nanoparticles via co-precipitation method. The characterization of nano composite is carried out through Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) and Thermo-gravimetric analysis (TGA) resulting less than 10 μm cellulose fiber and approx. 50 nm ZnO NPs. Zinc oxide impregnated cellulose (ZnO-Cel) exhibited significant bacterial devastation property when compared to ZnO NPs or Cellulose via disc diffusion and colony forming unit methods. In addition, the ZnO-Cel exhibited significant total antioxidant, and minor DPPH free radical scavenging and total reducing power activities. The nano composite also showed time dependent increase in photocatalytic by effectively degrading methylene blue dye up to 69.5% under sunlight irradiation within 90 min. The results suggest effective utilization of cellulose obtained from citrus waste and synthesis of pharmacologically important nano-composites that can be exploited in wound dressing; defence against microbial attack and healing due to antioxidative property, furthermore can also be used for waste water treatment.

  5. Synthesis of Boron Nitride Nanotubes for Engineering Applications

    NASA Technical Reports Server (NTRS)

    Hurst, Janet; Hull, David; Gorican, Dan

    2005-01-01

    Boron Nitride nanotubes (BNNT) are of interest to the scientific and technical communities for many of the same reasons that carbon nanotubes (CNT) have attracted large amounts of attention. Both materials have potentially unique and significant properties which may have important structural and electronic applications in the future. However of even more interest than their similarities may be the differences between carbon and boron nanotubes. Whilt boron nitride nanotubes possess a very high modulus similaar to CNT, they are also more chemically and thermally inert. Additionally BNNT possess more uniform electronic properties, having a uniform band gap of approximately 5.5 eV while CNT vary from semi-conductin to conductor behavior. Boron Nitride nanotubes have been synthesized by a variety of methods such as chemical vapor deposition, arc discharge and reactive milling. Consistently producing a reliable product has proven difficult. Progress in synthesis of 1-2 gram sized batches of Boron Nitride nanotubes will be discussed as well as potential uses for this unique material.

  6. Scalable synthesis and energy applications of defect engineeered nano materials

    NASA Astrophysics Data System (ADS)

    Karakaya, Mehmet

    Nanomaterials and nanotechnologies have attracted a great deal of attention in a few decades due to their novel physical properties such as, high aspect ratio, surface morphology, impurities, etc. which lead to unique chemical, optical and electronic properties. The awareness of importance of nanomaterials has motivated researchers to develop nanomaterial growth techniques to further control nanostructures properties such as, size, surface morphology, etc. that may alter their fundamental behavior. Carbon nanotubes (CNTs) are one of the most promising materials with their rigidity, strength, elasticity and electric conductivity for future applications. Despite their excellent properties explored by the abundant research works, there is big challenge to introduce them into the macroscopic world for practical applications. This thesis first gives a brief overview of the CNTs, it will then go on mechanical and oil absorption properties of macro-scale CNT assemblies, then following CNT energy storage applications and finally fundamental studies of defect introduced graphene systems. Chapter Two focuses on helically coiled carbon nanotube (HCNT) foams in compression. Similarly to other foams, HCNT foams exhibit preconditioning effects in response to cyclic loading; however, their fundamental deformation mechanisms are unique. Bulk HCNT foams exhibit super-compressibility and recover more than 90% of large compressive strains (up to 80%). When subjected to striker impacts, HCNT foams mitigate impact stresses more effectively compared to other CNT foams comprised of non-helical CNTs (~50% improvement). The unique mechanical properties we revealed demonstrate that the HCNT foams are ideally suited for applications in packaging, impact protection, and vibration mitigation. The third chapter describes a simple method for the scalable synthesis of three-dimensional, elastic, and recyclable multi-walled carbon nanotube (MWCNT) based light weight bucky-aerogels (BAGs) that are

  7. Highly Selective Synthesis of Halomon, Plocamenone, and Isoplocamenone

    PubMed Central

    Bucher, Cyril; Deans, Richard M.; Burns, Noah Z.

    2015-01-01

    Over 160 chiral vicinal bromochlorinated natural products have been identified, however a lack of synthetic methods for the selective incorporation of halogens into organic molecules has hindered their synthesis. Here we disclose the first total synthesis and structural confirmation of isoplocamenone and plocamenone, as well as the first selective and scaleable synthesis of the preclinical anticancer natural product halomon. The synthesis of these interhalogenated compounds has been enabled by our recently developed chemo-, regio-, and enantioselective dihalogenation reaction. PMID:26394844

  8. Synthesis, characterizations, and applications of carbon nanotubes and silicon nanowires

    NASA Astrophysics Data System (ADS)

    Xiong, Guangyong

    Carbon nanotubes (CNTs) have received great attention because of their unique structure and promising applications in microelectronic devices such as field electron emitters. Silicon nanowires (SiNWs) are also very popular because Si is a well established electronic material. This thesis will present my effort on synthesis, characterizations, and applications of CNTs and SiNWs by thermal chemical vapor deposition (CVD) method. For CNTs growth, block copolymer micelles were used as a template to create large area arrays of metal nanoclusters as catalysts for patterned arrays, and Fe/Al/Fe sandwich film on single crystal magnesium oxide (MgO) substrate was used as the catalyst for growth of long length aligned CNTs by CVD. The factors that affect the structure and length of CNTs have been investigated. CNTs were also grown on etched Si substrate by PECVD method. Continuous dropwise condensation was achieved on a biomimetic two-tier texture with short CNTs deposited on micromachined pillars. Superhydrophobic condensation model was studied. For SiNWs growth, hydrogen gold tetrachloride was uniformly mixed into the salt and decomposed into gold nanoparticles at the growth temperature and acted as the catalyst particles to start the growth of Si nanowires. The as-grown Si nanowires are about 70--90 nm in diameter and up to 200 micrometers long. The salt was completely removed by water rinse after growth. Field emission of aligned CNTs grown on Si substrates and SiNWs on Si substrates and carbon clothes has been studied. A post growth annealing procedure has been found to drastically improve the field emission performance of these CNTs and SiNWs.

  9. Synthesis and characterization of advanced nanomaterials for energy applications

    NASA Astrophysics Data System (ADS)

    Xie, Ming

    Energy is essential for life. It is thus important to continue understanding how to reduce energy consumption, and increase energy generation. The use of nanoscale materials (nanomaterials) are expected to reduce resources and energy needed in fabricating electrical and electronic devices and help in reducing energy consumption. For example, boron nitride nanotubes (BNNTs) which have uniform band structures, are expected to find application in nanoscale electronic and optoelectronic devices. These devices will have smaller dimension, cost fewer resources and less energy to fabricate, and consume less energy due to minimum electron scattering in their ideally defect-free tubular structures. On the other hand, nanomaterials are also expected to improve the performance of thermoelectric devices that can convert heat into energy. In this thesis, we first investigated low-temperature synthesis of BNNTs (Chapter 1). Effects of substrate temperatures, bias voltages, and catalysts are discussed and a selective-phase growth model is proposed. During the course of this investigation, we discovered Si nanotubes (SiNTs) by catalytic plasma treatment (Chapter 2). The detailed growth parameters and characterizations are presented and a modified growth model is discussed. In addition, electronic properties are measured by AFM. Since Si has exceptional thermoelectric properties, the newly discovered SiNTs are prospects for related applications. We have thus evaluated the potential conversion efficiency and production cost of various nanostructured thermoelectric materials (Chapter 3 and 4). Based on state-of-the-art dish-stirling systems, we evaluate the feasibility of replacing stirling engines by thermoelectric modules. Finally, we have decided to investigate the properties of boron-nanocarbon ensembles (Chapter 5 and 6) as prospective thermoelectric materials. Detailed characterizations includes SEM, HRTEM, Raman, XRD are presented. Seebeck coefficient and electrical

  10. Synthesis and Characterization of Dyes with Solar Energy Applications

    NASA Astrophysics Data System (ADS)

    Brennan, Bradley J.

    The sun provides Earth with a virtually limitless source of energy capable of sustaining all of humanity's needs. Photosynthetic organisms have exploited this energy for eons. However, efficiently converting solar radiation into a readily available and easily transportable form is complex. New materials with optimized physical, electrochemical, and photophysical properties are at the forefront of organic solar energy conversion research. In the work presented herein, porphyrin and organometallic dyes with widely-varied properties were studied for solar energy applications. In one project, porphyrins and porphyrin-fullerene dyads with aniline-like features were polymerized via electrochemical methods into semiconductive thin films. These were shown to have high visible light absorption and stable physical and electrochemical properties. However, experimentation using porphyrin polymer films as both the light absorber and semiconductor in a photoelectrochemical cell showed relatively low efficiency of converting absorbed solar energy into electricity. In separate work, tetra-aryl porphyrin derivatives were examined in conjunction with wide-bandgap semiconductive oxides TiO2 and SnO2. Carboxylic acid-, phosphonic acid-, and silatrane-functionalized porphyrins were obtained or synthesized for attachment to the metal oxide species. Electrochemical, photophysical, photoelectrochemical, and surface stability studies of the porphyrins were performed for comparative purposes. The order of surface linkage stability on TiO2 in alkaline conditions, from most stable to least, was determined to be siloxane > phosphonate > carboxylate. Finally, porphyrin dimers fused via their meso and beta positions were synthesized using a chemical oxidative synthesis with a copper(II) oxidant. The molecules exhibit strong absorption in the visible and near-infrared spectral regions as well as interesting electrochemical properties suggesting possible applications in light harvesting and redox

  11. Patterns in Organometallic Chemistry with Application in Organic Synthesis.

    ERIC Educational Resources Information Center

    Schwartz, Jeffrey; Labinger, Jay A.

    1980-01-01

    Of interest in this discussion of organometallic complexes are stoichiometric or catalytic reagents for organic synthesis in the complex transformations observed during synthesis for transition metal organometallic complexes. Detailed are general reaction types from which the chemistry or many transition metal organometallic complexes can be…

  12. Synthesis and properties of unagglomerated nanocomposite particles for nanomedical applications

    NASA Astrophysics Data System (ADS)

    Rouse, Sarah M.

    2005-11-01

    Methods have been developed to prepare stable, unagglomerated active-medical-agent nanoparticles in a range of sizes, based on reverse-micelle microemulsion techniques. The process used to prepare monodisperse, spherical nanocomposite particles is based on methods originally outlined in detail by Adair et al. and Li et al. The "Molecular Dot" (MD) nanoparticles incorporate a variety of medically-active substances, such as organic fluorophores and therapeutic drugs, internally distributed in silica, titania, calcium phosphate, or calcium phospho-silicate matrices. The synthesis techniques have also been modified to produce nanoparticles containing combinations of fluorophores and medicinal agents, in order to monitor drug release and location. The specific biomedical application for the nanocomposite particles dictates the selection of core and shell-matrix materials. For example, the protective shell-matrices of the silica and titania MDs shield the active-medical agents from damage due to changes in pH, temperature, and other environmental effects. Conversely, the calcium phosphate and calcium phospho-silicate shell-matrix nanoparticles can potentially be engineered to dissolve in physiological environments. The method used to remove residual precursor materials while maintaining a well-dispersed assembly of nanoparticles is critical to the use of nanocolloids in medical applications. The dispersion approach is based on protection-dispersion theory tailored to accommodate the high surface areas and reactivity of sub-50 nm particles in aqueous or water/ethanol mixtures. Dispersion of the nanocomposite particles is further enhanced with the use of size-exclusion high performance liquid chromatography (HPLC) to simultaneously wash and disperse the nanocomposite particle suspensions. The state of dispersion of the nanosuspensions is evaluated using the average agglomeration number (AAN) approach in conjunction with other characterization techniques. The formulation of

  13. Synthesis and applications of electrically conducting polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Ku, Bon-Cheol

    This research focuses on the synthesis and applications of electrically conducting polymer nanocomposites through molecular self-assembly. Two different classes of polymers, polyaniline (PANI) and polyacetylenes have been synthesized by biomimetic catalysis and spontaneous polymerization method. For gas barrier materials, commercially available polymers, poly(allylamine hydrochloride) (PAH) and poly (acrylic acid) (PAA), have also been used and thermally cross-linked. The morphological, optical and electrical properties of amphiphilic polyacetylenes have been studied. Furthermore, barrier properties, permselectivity, pervaporation properties of polyacetylenes/aluminosilicate nanocomposites have been investigated. For processability and electrical properties of carbon nanotube and conducting polymers, substituted ionic polyacetylenes (SIPA) have been covalently incorporated onto single-walled carbon nanotubes (SWNT) using the "grafting-from" technique. In the first study, a nanocomposite film catalyst has been prepared by electrostatic layer-by-layer (ELBL) self-assembly of a polyelectrolyte and a biomimetic catalyst for synthesis of polyaniline. Poly(dimethyl diallylammonium chloride) (PDAC) and hematin have been used as polycation and counter anions, respectively. The absorption spectra by UV-vis-NIR spectroscopy showed that conductive form polyaniline was formed not only as a coating on the surface of the ELBL composites but was also formed in solution. Furthermore, it was found that the reaction rate was affected by pH and concentration of hematin in the multilayers. The feasibility of controlled desorption of hematin molecules from the LBL assembly was explored and demonstrated by changing the pH and hematin concentration. The polymerization rate of aniline in solution was enhanced with decreasing pH of the solutions due to increased desorption of hematin nanoparticles from the multilayers. These ELBL hematin assemblies demonstrated both a way to functionalize

  14. Synthesis, assembly, and applications of single-walled carbon nanotube

    NASA Astrophysics Data System (ADS)

    Ryu, Koungmin

    This dissertation presents the synthesis and assembly of aligned carbon nanotubes, and their applications in both nano-electronics such as transistor and integrated circuits and macro-electronics in energy conversion devices as transparent conducting electrodes. Also, the high performance chemical sensor using metal oxide nanowire has been demonstrated. Chapter 1 presents a brief introduction of carbon nanotube, followed by discussion of a new synthesis technique using nanosphere lithography to grow highly aligned single-walled carbon nanotubes atop quartz and sapphire substrates. This method offers great potential to produce carbon nanotube arrays with simultaneous control over the nanotube orientation, position, density, diameter and even chirality. Chapter 3 introduces the wafer-scale integration and assembly of aligned carbon nanotubes, including full-wafer scale synthesis and transfer of massively aligned carbon nanotube arrays, and nanotube device fabrication on 4 inch Si/SiO2 wafer to yield submicron channel transistors with high on-current density ˜ 20 muA/mum and good on/off ratio and CMOS integrated circuits. In addition, various chemical doping methods for n-type nanotube transistors are studied to fabricate CMOS integrated nanotube circuits such as inverter, NAND and NOR logic devices. Furthermore, defect-tolerant circuit design for NAND and NOR is proposed and demonstrated to guarantee the correct operation of logic circuit, regardless of the presence of mis-aligned or mis-positioned nanotubes. Carbon nanotube flexible electronics and smart textiles for ubiquitous computing and sensing are demonstrated in chapter 4. A facile transfer printing technique has been introduced to transfer massively aligned single-walled carbon nanotubes from the original sapphire/quartz substrates to virtually any other substrates, including glass, silicon, polymer sheets, and even fabrics. The characterization of transferred nanotubes reveals that the transferred

  15. Enantioselective sorption of the chiral fungicide metalaxyl on soil from non-racemic aqueous solutions: Environmental implications.

    PubMed

    Celis, Rafael; Gámiz, Beatriz; Facenda, Gracia; Hermosín, María C

    2015-12-30

    Mechanisms governing the enantioselectivity of the processes that determine the behavior of chiral pollutants in the environment need to be better understood. Understanding these mechanisms should help improve predictions of the hazards and risks chiral compounds can pose to people and the environment. We report the results of batch sorption experiments indicating that the sorption of the chiral fungicide metalaxyl on soil from non-racemic initial solutions was enantioselective. While from a racemic initial solution the two enantiomers of metalaxyl were sorbed on the soil to the same extent, increasing the fraction of R-enantiomer in the initial solution led to enhanced sorption of this enantiomer and to reduced sorption of the S-enantiomer. Considering the shape of the sorption isotherms (S-type) and the sorption behavior of model sorbents, we attributed this effect to molecular interactions between metalaxyl enantiomer species at the sorbed state, where R-R metalaxyl interactions appeared to be more favorable than R-S metalaxyl interactions. We discuss important environmental implications of the proposed mechanism, such as those related to the fact that the biological degradation of metalaxyl is known to be an enantioselective process that can yield non-racemic residues in soils shortly after application of the fungicide as a racemic mixture.

  16. Whole cells in enantioselective reduction of benzyl acetoacetate

    PubMed Central

    Ribeiro, Joyce Benzaquem; Ramos, Aline de Souza; Lopes, Raquel de Oliveira; da Silva, Gabriela Veloso Vieira; de Souza, Rodrigo Octavio Mendonça Alves

    2014-01-01

    The β-ketoester benzyl acetoacetate was enantioselectively reduced to benzyl (S)-3-hydroxybutanoate by seven microorganism species. The best result using free cells was obtained with the yeast Hansenula sp., which furnished 97% ee and 85% of conversion within 24 h. After immobilization in calcium alginate spheres, K.marxianus showed to be more stable after 2 cycles of reaction. PMID:25477927

  17. Pyrones to Pyrans: Enantioselective Radical Additions to Acyloxy Pyrones

    PubMed Central

    Sibi, Mukund P.; Zimmerman, Jake

    2008-01-01

    This manuscript describes a highly site, diastereo-, and enantioselective intermolecular radical addition/hydrogen atom transfer to hydroxypyrones pyromeconic and kojic acids. The methodology can be extended to the formation of chiral quaternary centers. The products obtained are densely functionalized pyran moieties. The products contain structural features amenable for the introduction of additional substituents. PMID:17031933

  18. Enantioselective Claisen rearrangements with a hydrogen-bond donor catalyst.

    PubMed

    Uyeda, Christopher; Jacobsen, Eric N

    2008-07-23

    N,N'-Diphenylguanidinium ion associated with the noncoordinating BArF counterion is shown to be an effective catalyst for the [3,3]-sigmatropic rearrangement of a variety of substituted allyl vinyl ethers. Highly enantioselective catalytic Claisen rearrangements of ester-substituted allyl vinyl ethers are then documented using a new C2-symmetric guanidinium ion derivative. PMID:18576616

  19. CHLORDANE AND HEPTACHLOR ARE METABOLIZED ENANTIOSELECTIVELY BY RAT LIVER MICROSOMES

    PubMed Central

    Kania-Korwel, Izabela; Lehmler, Hans-Joachim

    2013-01-01

    Chlordane, heptachlor and their metabolites are chiral persistent organic pollutants that undergo enantiomeric enrichment in the environment. This study investigated the enantioselective metabolism of both chlordane isomers and heptachlor, major components of technical chlordane, by liver microsomes prepared from male rats treated with corn oil (CO) or inducers of CYP2B (PB; Phenobarbital) and CYP3A enzymes (DX; dexamethasone), isoforms induced by chlordane treatment. The extent of the metabolism of all three parent compounds was dependent on the microsomal preparation used, and followed the rank order PB > DX > CO. The mass balances ranged from 49-130 % of the parent compound added to the microsomal incubations. Both cis- and trans-chlordane were enantioselectively metabolized to oxychlordane (EF=0.45-0.89) and 1,2-dichlorochlordene (EF=0.42-0.90). Heptachlor was metabolized enantioselectively, with heptachlor epoxide B (EF=0.44-0.54) being the only metabolite. Interestingly, the direction on the enrichment for oxychlordane, 1,2-dichlorochlordene and heptachlor epoxide differed depending on the microsomal preparation. These findings demonstrate that the direction and extent of the enantioselective metabolism of both chlordane isomers and heptachlor is P450 isoform-dependent and can be modulated by the induction of P450 enzymes. PMID:23799267

  20. Catalytic, Enantioselective, Intramolecular Carbosulfenylation of Olefins. Preparative and Stereochemical Aspects

    PubMed Central

    Denmark, Scott E.; Jaunet, Alex

    2014-01-01

    The first catalytic, enantioselective, intramolecular carbosulfenylation of isolated alkenes with aromatic nucleophiles is described. The combination of N-phenylsulfenylphthalimide, a chiral selenophosphoramide derived from BINAM, and ethanesulfonic acid as a co-catalytic Brønsted acid induced an efficient and selective cyclofunctionalization of various alkenes (aliphatic and aromatic) tethered to a 3,4-methylenedioxyphenyl ring. Under these conditions, 6-phenylthio-5,6,7,8-tetrahydronaphthalenes are formed diastereospecifically in good yields (50–92%) and high enantioselectivities (71:29 – 97:3 er). E-Alkenes reacted much more rapidly and with much higher selectivity than Z-alkenes, whereas electron rich alkenes reacted more rapidly but with comparable selectivity to electron-neutral alkenes and electron deficient alkenes. The Brønsted acid played a critical role in effecting reproducible enantioselectivity. A model for the origin of enantioselectivity and the dependence of rate and selectivity on alkene structure is proposed along with a rationale for the site selectivity in reactions with mono-activated arene nucleophiles. PMID:24328051