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Sample records for enantioselective synthesis application

  1. Enantioselective Synthesis of (+)-Majusculone

    PubMed Central

    Taber, Douglass F.; Sikkander, M. Inthikhab; Storck, Pierre H.

    2011-01-01

    The first enantioselective synthesis of a chamigrane sesquiterpene, (+)-majusculone, has been completed. The quaternary center was generated asymmetrically by alkylidene carbene insertion, with retention of absolute configuration, from a diastereomerically pure ketal. PMID:17447815

  2. Enantioselective synthesis of (-)-basiliskamide A.

    PubMed

    Chen, Ming; Roush, William R

    2012-03-16

    Basiliskamide A is an antifungal polyketide natural product isolated by Andersen and co-workers from a Bacillus laterosporus isolate, PNG-276. A nine-step enantioselective synthesis of (-)-basiliskamide A is reported, starting from commercially available β-hydroxy ester 7. The synthesis features a highly diastereoselective mismatched double asymmetric δ-stannylallylboration reaction of aldehyde 5 with the bifunctional allylborane reagent 4.

  3. 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

  4. Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.

    2010-01-01

    An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium–catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper–catalyzed enantioselective conjugate reduction of a β-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented. PMID:16178549

  5. Enantioselective synthesis of (+)-royleanone from sulfinyl quinones.

    PubMed

    Carreño, M C; García Ruano, J L; Toledo, M A

    2000-01-01

    A convergent enantioselective synthesis of (+)-royleanone (1) is described starting from enantiomerically pure (S)-3-hydroxy-2-isopropyl-5-tert-butylsulfinyl-p-benzoquinone, which is readily available from 3-isopropyl-1,2,4-trimethoxybenzene and 1,3,3-trimethyl-2-vinylcyclohexene. The key step is a tandem asymmetric Diels-Alder reaction/pyrolytic sulfoxide elimination process.

  6. Enantioselective Synthesis of Cephalimysins B and C.

    PubMed

    Chalupa, David; Vojáčková, Petra; Partl, Jiří; Pavlović, Dražen; Nečas, Marek; Švenda, Jakub

    2017-02-17

    The first synthesis of cephalimysins B and C is reported. The route features a Ni(II)-diamine-catalyzed enantioselective conjugate addition of a densely substituted 3(2H)-furanone and an efficient dihydroxylation-lactonization sequence as key steps in the assembly of the spirocyclic core. The fully synthetic strategy is amenable to analog preparation.

  7. Enantioselective Synthesis of (−)-Acetylapoaranotin

    PubMed Central

    2017-01-01

    The first enantioselective total synthesis of the epipolythiodiketopiperazine (ETP) natural product (−)-acetylapoaranotin (3) is reported. The concise synthesis was enabled by an eight-step synthesis of a key cyclohexadienol-containing amino ester building block. The absolute stereochemistry of both amino ester building blocks used in the synthesis is set through catalytic asymmetric (1,3)-dipolar cycloaddition reactions. The formal syntheses of (−)-emethallicin E and (−)-haemotocin are also achieved through the preparation of a symmetric cyclohexadienol-containing diketopiperazine. PMID:28349698

  8. Cu(II)-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: application in the enantioselective synthesis of orphenadrine and neobenodine.

    PubMed

    Sui, Yao-Zong; Zhang, Xi-Chang; Wu, Jun-Wen; Li, Shijun; Zhou, Ji-Ning; Li, Min; Fang, Wenjun; Chan, Albert S C; Wu, Jing

    2012-06-11

    With certain amounts of sodium tert-butoxide and tert-butanol as additives, catalytic amounts of an inexpensive and easy-to-handle copper source Cu(OAc)(2)⋅H(2)O, a commercially available and air-stable non-racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96 %). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine.

  9. Synthesis of rare earth catalysts and their applications for enantioselective synthesis of heterocyclic β-amino alcohols.

    PubMed

    Martin, Myriam; El Hellani, Ahmad; Yang, Jing; Collin, Jacqueline; Bezzenine-Lafollée, Sophie

    2011-12-02

    A new family of chiral lanthanide complexes derived from (R)-binaphthol has been synthesized by a one-pot procedure using only commercially available substrates. These complexes were evaluated for the aminolysis of meso-epoxides and proved to be efficient enantioselective catalysts. The samarium complex coordinated by two (R)-binaphthoxide ligands was the most enantioselective catalyst of this series. β-Amino alcohols including heterocycles have been isolated with enantiomeric excesses up to 84%.

  10. Enantioselective synthesis of (+)- and (-)-dihydroepiepoformin and (+)-epiepoformin.

    PubMed

    Carreño, M Carmen; Merino, Estíbaliz; Ribagorda, María; Somoza, Alvaro; Urbano, Antonio

    2005-03-31

    [reaction: see text] The enantioselective synthesis of both enantiomers of dihydroepiepoformin (1) and (+)-epiepoformin (2) was achieved from (p-tolylsulfinyl)methyl-p-quinols (SR)- or (SS)-3 and (4R,SR)-4, respectively. Key features include the stereocontrolled conjugate addition of AlMe3 to p-quinol 3 and retrocondensation to the ketone functionality, previous to oxidation of the beta-hydroxy sulfoxide moiety of advanced intermediates to the corresponding sulfone.

  11. An Enantioselective Synthesis of Beta-Eudesmol.

    DTIC Science & Technology

    1986-01-01

    whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgement the proposed use ...bicyclic sesquiterpene which is - commonly found in nature. It has been a synthetic target for many researchers, most of whom used approaches based on...keudesmol. -We hi4ve 4eveloped-an enantioselective synthesis of 00 ,~eudesmol using diastereoselective cyclopropanation to install the O- -Q’t A 4a

  12. Catalytic enantioselective synthesis of quaternary carbon stereocentres.

    PubMed

    Quasdorf, Kyle W; Overman, Larry E

    2014-12-11

    Quaternary carbon stereocentres-carbon atoms to which four distinct carbon substituents are attached-are common features of molecules found in nature. However, before recent advances in chemical catalysis, there were few methods of constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules. This progress now makes it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials.

  13. Catalytic enantioselective synthesis of quaternary carbon stereocentres

    NASA Astrophysics Data System (ADS)

    Quasdorf, Kyle W.; Overman, Larry E.

    2014-12-01

    Quaternary carbon stereocentres--carbon atoms to which four distinct carbon substituents are attached--are common features of molecules found in nature. However, before recent advances in chemical catalysis, there were few methods of constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for the synthesis of single stereoisomers of such organic molecules. This progress now makes it possible to incorporate quaternary stereocentres selectively in many organic molecules that are useful in medicine, agriculture and potentially other areas such as flavouring, fragrances and materials.

  14. Enantioselective synthesis of pactamycin, a complex antitumor antibiotic.

    PubMed

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

    2013-04-12

    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 antiproliferative properties across multiple phylogenetic domains, but it 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. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and 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 15 steps and is immediately amenable for structural analog synthesis.

  15. Enantioselective Synthesis of β-Arylamines via Chiral Phosphoric Acid-Catalyzed Asymmetric Reductive Amination.

    PubMed

    Kim, Kyung-Hee; Lee, Chun-Young; Cheon, Cheol-Hong

    2015-06-19

    A new method for the synthesis of chiral β-aryl amines via chiral phosphoric acid-catalyzed enantioselective reductive amination of benzyl methyl ketone derivatives with Hantzsch ester was developed. Various chiral β-aryl amines were obtained in high yields and with good to high enantioselectivities. This transformation is applicable to gram-scale reactions, and the catalyst loading can be reduced to 1 mol % without sacrificing any catalytic efficacy. Furthermore, the resulting β-aryl amine was successfully converted into a tetrahydroisoquinoline compound without any loss of enantioselectivity.

  16. Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)-Verapamil.

    PubMed

    Oliveira, Caio C; Pfaltz, Andreas; Correia, Carlos Roque Duarte

    2015-11-16

    We describe herein a highly regio- and enantioselective Pd-catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all-carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine- and pyrazino-oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantiomeric ratios up to >99:1. Both linear and branched substituents on the olefins were well-tolerated. The potential of this new method is demonstrated by the straightforward synthesis of several O-methyl lactols and lactones containing quaternary stereocenters, together with a concise enantioselective total synthesis of the calcium channel blocker verapamil.

  17. 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

  18. A Concise Enantioselective Synthesis of (−)-Ranirestat

    PubMed Central

    Trost, Barry M.; Osipov, Maksim; Dong, Guangbin

    2010-01-01

    A concise, enantioselective synthesis of the potent aldose reductase inhibitor ranirestat (1) is reported. The synthesis was accomplished employing inexpensive, commercially available starting materials. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of malonate 4 was utilized as a key transformation to construct the tetrasubstituted chiral center in the target. PMID:20148531

  19. Enantioselective synthesis of trifluoromethyl-substituted cyclopropanes.

    PubMed

    Denton, Justin R; Sukumaran, Dinesh; Davies, Huw M L

    2007-07-05

    The reaction of 1-aryl-2,2,2-trifluorodiazoethanes with alkenes, catalyzed by the adamantylglycine-derived dirhodium complex Rh2(R-PTAD)4, generates trifluoromethyl-substituted cyclopropanes with high diastereoselectivity (>94%) and enantioselectivity (88->98%).

  20. 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.

  1. Enantioselective synthesis of tunable chiral Clickphine P,N-ligands and their application in Ir-catalyzed asymmetric hydrogenation.

    PubMed

    Wassenaar, Jeroen; Detz, Remko J; de Boer, Sandra Y; Lutz, Martin; van Maarseveen, Jan H; Hiemstra, Henk; Reek, Joost N H

    2015-04-03

    A small library of highly tunable chiral Clickphine P,N-ligands has been prepared in an enantioselective fashion by Cu(I)-catalyzed asymmetric propargylic amination using a single chiral complex and a subsequent in situ cycloaddition click reaction. The scope of the propargylic amination to yield optically active triazolyl amines is described. The amines are transformed in a one-pot procedure to the corresponding Ir-Clickphine complexes, which serve as catalysts for the asymmetric hydrogenation of di-, tri-, and tetrasubstituted unfunctionalized alkenes. Enantioselectivities of up to 90% ee were obtained in these hydrogenations, which are among the best reported in the case of the tetrasubstituted substrate 2-(4'-methoxyphenyl)-3-methylbut-2-ene (9) (87% ee). This is a demonstration of the effective use of the chiral pool, as from one chiral catalyst a library of chiral Ir complexes has been synthesized that can hydrogenate various alkenes with high selectivity.

  2. Enantioselective synthesis of alkaloids from phenylglycinol-derived lactams.

    PubMed

    Amat, Mercedes; Llor, Núria; Griera, Rosa; Pérez, Maria; Bosch, Joan

    2011-04-01

    This review is focused on recent synthetic achievements and ongoing work in our laboratory using phenylglycinol-derived oxazolopiperidone lactams as starting materials for the enantioselective synthesis of piperidine-containing alkaloids: madangamines, 2,5-disubstituted decahydroquinoline and 1-substituted tetrahydroisoquinoline alkaloids, the indole alkaloids 20S- and 20R-dihydrocleavamine and quebrachamine, and indole alkaloids of the uleine and silicine groups.

  3. Enantioselective Synthesis and Application to the Allylic Imidate Rearrangement of Amine-Coordinated Palladacycle Catalysts of Cobalt Sandwich Complexes

    PubMed Central

    Cassar, Doyle J; Ilyashenko, Gennadiy; Ismail, Muhammad; Woods, James; Hughes, David L; Richards, Christopher J

    2013-01-01

    The reaction of (η5-(N,N-dimethylaminomethyl)cyclopentadien-yl)(η4-tetraphenylcyclobutadiene)cobalt with sodium tetrachloropalladate and (R)-N-acetylphenylalanine gave planar chiral palladacycle di-μ-chloridebis[(η5-(Sp)-2-(N,N-dimethylaminomethyl)cyclopentadienyl,1-C,3′-N)(η4-tetraphenylcyclobutadiene)cobalt]dipalladium [(Sp)-Me2-CAP-Cl] in 92 % ee and 64 % yield. Enantiopurity (>98 % ee) was achieved by purification of the monomeric (R)-proline adducts and conversion back to the chloride dimer. Treatment with AgOAc gave (Sp)-Me2-CAP-OAc which was applied to asymmetric transcyclopalladation (up to 78 % ee). The (R)-N-acetylphenylalanine mediated palladation methodology was applicable also to the corresponding N,N-diethyl (82 % ee, 39 % yield) and pyrrolidinyl (>98 % ee, 43 % yield) cobalt sandwich complexes. A combination of 5 mol % of the latter [(Sp)-Pyrr-CAP-Cl] and AgNO3 (3.8 equiv) is a catalyst for the allylic imidate rearrangement of an (E)-N-aryltrifluoroacetimidate (up to 83 % ee), and this catalyst system is also applicable to the rearrangement of a range of (E)-trichloroacetimidates (up to 99 % ee). This asymmetric efficiency combined with the simplicity of catalyst synthesis provides accessible solutions to the generation of non-racemic allylic amine derivatives. PMID:24264943

  4. 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

    2014-02-05

    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.

  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. Organocatalytic Enantioselective Synthesis of 1,4-Dioxanes and Other Oxa-Heterocycles by Oxetane Desymmetrization.

    PubMed

    Yang, Wen; Sun, Jianwei

    2016-01-26

    A new asymmetric synthesis of chiral 1,4-dioxanes and other oxa-heterocycles has been developed by means of organocatalytic enantioselective desymmetrization of oxetanes. This mild process proceeds with exceedingly high efficiency and enantioselectivity to establish the quaternary stereocenters. This method complements the existing, yet limited, strategies for the synthesis of these oxa-heterocycles.

  7. 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

  8. Enantioselective Synthesis of Strobamine and its Analogues

    DTIC Science & Technology

    2010-01-01

    using likelihood methods in PLATON .6,7 Based on the analysis of 1077 Bijvoet pairs (90% coverage), this analysis indicated that the absolute structure...Majewski, M.; Lazny, R. J. Org. Chem. 1995, 60, 5825. 5. Olah, G. A.; Arvanaghi, M.; Prakash, G. K. S. Synthesis 1983, 636. 6. Spek, A. L. PLATON

  9. 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.

  10. Enantioselective palladium-catalyzed dearomative cyclization for the efficient synthesis of terpenes and steroids.

    PubMed

    Du, Kang; Guo, Pan; Chen, Yuan; Cao, Zhen; Wang, Zheng; Tang, Wenjun

    2015-03-02

    A novel enantioselective palladium-catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all-carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (-)-totaradiol.

  11. 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

  12. 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.

  13. Enantioselective Total Synthesis of (−)-Acutumine

    PubMed Central

    Li, Fang; Tartakoff, Samuel S.; Castle, Steven L.

    2009-01-01

    An account of the total synthesis of the tetracyclic alkaloid (−)-acutumine is presented. A first-generation approach to the spirocyclic subunit was unsuccessful due to incorrect regioselectivity in a radical cyclization. However, this work spawned a second-generation strategy in which the spirocycle was fashioned via a radical–polar crossover reaction. This process merged an intramolecular radical conjugate addition with an enolate hydroxylation, and created two stereocenters with excellent diastereoselectivity. The reaction was promoted by irradiation with a sunlamp, and a ditin reagent was required for aryl radical formation. These facts suggest that the substrate may function as a sensitizer, thereby facilitating homolytic cleavage of the ditin reagent. The propellane motif of the target was then installed via annulation of a pyrrolidine ring onto the spirocycle. The sequence of reactions used included a phenolic oxidation, an asymmetric ketone allylation mediated by Nakamura’s chiral allylzinc reagent, an anionic oxy-Cope rearrangement, a one-pot ozonolysis–reductive amination, and a Lewis acid promoted cyclization of an amine onto an α,β-unsaturated dimethyl ketal. Further studies of the asymmetric ketone allylation demonstrated the ability of the Nakamura reagent to function well in a mismatched situation. A TiCl4-catalyzed regioselective methyl enol etherification of a 1,3-diketone completed the synthesis. PMID:19904909

  14. The first enantioselective organocatalytic Mukaiyama-Michael reaction: a direct method for the synthesis of enantioenriched gamma-butenolide architecture.

    PubMed

    Brown, Sean P; Goodwin, Nicole C; MacMillan, David W C

    2003-02-05

    The first enantioselective organocatalytic Mukaiyama-Michael reaction using alpha,beta-unsaturated aldehydes has been accomplished. The use of iminium catalysis has provided a new strategy for the enantioselective addition of 2-silyloxy furans to unsaturated aldehydes to generate a variety of butenolide systems, an important chiral synthon found among many natural isolates. The (2S,5S)-5-benzyl-2-tert-butyl-imidazolidinone amine catalyst has been found to mediate the conjugate addition of a wide variety of substituted and unsubstituted silyloxy furans to unsaturated aldehydes. A diverse range of aldehyde substrates can be accommodated in this new organocatalytic transformation. Application of this new asymmetric technology to the enantioselective total synthesis of spiculisporic acid and the corresponding 5-epi-spiculisporic acid analogue is also discussed.

  15. Organocatalytic Michael and Friedel-Crafts reactions in enantioselective synthesis of biologically active compounds

    NASA Astrophysics Data System (ADS)

    Maltsev, O. V.; Beletskaya, Irina P.; Zlotin, Sergei G.

    2011-11-01

    Recent applications of organocatalytic Michael and Friedel-Crafts reactions in enantioselective synthesis of biologically active compounds: natural products, pharmaceutical agents and plant protection agents are reviewed. The key mechanisms of stereoinduction, types of organocatalysts and reagents used in these reactions are considered. The material is classified according to the type of newly formed bonds incorporating the asymmetric carbon atom, and the information for the most numerous C-C coupling reactions is systematized according to the natures of the electrophile and the nucleophile. The bibliography includes 433 references. Dedicated to Academician O M Nefedov on the occasion of his 80th birthday.

  16. Enantioselective synthesis of SSR 241586 by using an organo-catalyzed Henry reaction.

    PubMed

    Cochi, Anne; Métro, Thomas-Xavier; Pardo, Domingo Gomez; Cossy, Janine

    2010-08-20

    An organo-catalyzed Henry reaction, applied to an alpha-keto ester, has allowed the enantioselective synthesis of SSR 241586, a 2,2-disubstituted morpholine active in the treatment of schizophrenia and irritable bowel syndrome (IBS).

  17. Synthesis of chiral cyclic amines via Ir-catalyzed enantioselective hydrogenation of cyclic imines.

    PubMed

    Zhang, Ying; Kong, Duanyang; Wang, Rui; Hou, Guohua

    2017-04-05

    A highly enantioselective hydrogenation of cyclic imines for synthesis of chiral cyclic amines has been realized. With the complex of iridium and (R,R)-f-spiroPhos as the catalyst, a range of cyclic 2-aryl imines were smoothly hydrogenated under mild conditions without any additive to provide the corresponding chiral cyclic amines with excellent enantioselectivities of up to 98% ee. Moreover, this method could be successfully applied to the synthesis of (+)-(6S,10bR)-McN-4612-Z.

  18. Enantioselective Synthesis of Chiral Oxime Ethers: Desymmetrization and Dynamic Kinetic Resolution of Substituted Cyclohexanones.

    PubMed

    Nimmagadda, Sri Krishna; Mallojjala, Sharath Chandra; Woztas, Lukasz; Wheeler, Steven E; Antilla, Jon C

    2017-02-20

    Axially chiral cyclohexylidene oxime ethers exhibit unique chirality because of the restricted rotation of C=N. The first catalytic enantioselective synthesis of novel axially chiral cyclohexylidene oximes has been developed by catalytic desymmetrization of 4-substituted cyclohexanones with O-arylhydroxylamines and is catalyzed by a chiral BINOL-derived strontium phosphate with excellent yields and good enantioselectivities. In addition, chiral BINOL-derived phosphoric acid catalyzed dynamic kinetic resolution of α-substituted cyclohexanones has been performed and yields versatile intermediates in high yields and enantioselectivities.

  19. Synthesis of planar chiral phosphapalladacycles by highly enantioselective transcyclopalladation.

    PubMed

    Roca, Francesc X; Motevalli, Majid; Richards, Christopher J

    2005-03-02

    The first highly enantioselective synthesis of planar chiral ferrocene phosphapalladacycles was performed by high-yielding asymmetric transcyclopalladation with cobalt oxazoline palladacycles (COP). Use of di-mu-acetatobis[(eta5-(S)-(pR)-2-(2'-(4'-isopropyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II), followed by acetate/chloride ligand exchange, gave (pS)-di-mu-chloro[2-(2-dicyclohexylphosphino)phenylferroene-C1,P)dipalladium(II) (95% ee). Similarly, diastereomeric di-mu-acetatobis[(eta5-(S)-(pS)-2-(2'-(4'-tert-butyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II) led to the enantiomeric (pR)-phosphapalladacycle (95% ee), revealing the control of these reactions by the element of planar chirality in COP. The reactions were extended to the synthesis of (pS)- and (pR)-di-mu-chloro[2-(2-diphenylphosphino)phenylferroene-C1,P)dipalladium(II) (78 and 92% ee, respectively). In all cases, the palladium-free precursors to COP were recovered for recycling.

  20. Enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes.

    PubMed

    Chen, Weiliang; Cai, Yunfei; Fu, Xuan; Liu, Xiaohua; Lin, Lili; Feng, Xiaoming

    2011-09-16

    An enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes via a Knoevenagel/Pinner/Friedel-Crafts reaction of salicylaldehyde, malononitrile, and indole is presented. Moderate to good yields (up to 89%) and high enantioselectivities (up to 90% ee) were obtained with an N,N'-dioxide-Zn(II) complex as the catalyst. This strategy provides an efficient and convenient method to access enantiomerically enriched 2-amino-4H-chromene derivatives.

  1. Enantioselective N-heterocyclic carbene-catalyzed synthesis of trifluoromethyldihydropyridinones.

    PubMed

    Wang, Dong-Ling; Liang, Zhi-Qin; Chen, Kun-Quan; Sun, De-Qun; Ye, Song

    2015-06-05

    The enantioselective N-heterocyclic carbene-catalyzed [4 + 2] cyclocondensation of α-chloroaldehydes and trifluoromethyl N-Boc azadienes was developed, giving the corresponding 3,4-disubstituted-6-trifluoromethyldihydropyridin-2(1H)-ones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

  2. 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

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

    PubMed

    White, David E; Tadross, Pamela M; Lu, Zhe; Jacobsen, Eric N

    2014-07-08

    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.

  4. Graphene-based hybrid for enantioselective sensing applications.

    PubMed

    Zor, Erhan; Morales-Narváez, Eden; Alpaydin, Sabri; Bingol, Haluk; Ersoz, Mustafa; Merkoçi, Arben

    2017-01-15

    Chirality is a major field of research of chemical biology and is essential in pharmacology. Accordingly, approaches for distinguishing between different chiral forms of a compound are of great interest. We report on an efficient and generic enantioselective sensor that is achieved by coupling reduced graphene oxide with γ-cyclodextrin (rGO/γ-CD). The enantioselective sensing capability of the resulting structure was operated in both electrical and optical mode for of tryptophan enantiomers (D-/L-Trp). In this sense, voltammetric and photoluminescence measurements were conducted and the experimental results were compared to molecular docking method. We gain insight into the occurring recognition mechanism with selectivity toward D- and L-Trp as shown in voltammetric, photoluminescence and molecular docking responses. As an enantioselective solid phase on an electrochemical transducer, thanks to the different dimensional interaction of enantiomers with hybrid material, a discrepancy occurs in the Gibbs free energy leading to a difference in oxidation peak potential as observed in electrochemical measurements. The optical sensing principle is based on the energy transfer phenomenon that occurs between photoexcited D-/L-Trp enantiomers and rGO/γ-CD giving rise to an enantioselective photoluminescence quenching due to the tendency of chiral enantiomers to form complexes with γ-CD in different molecular orientations as demonstrated by molecular docking studies. The approach, which is the first demonstration of applicability of molecular docking to show both enantioselective electrochemical and photoluminescence quenching capabilities of a graphene-related hybrid material, is truly new and may have broad interest in combination of experimental and computational methods for enantiosensing of chiral molecules.

  5. 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

  6. 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.

  7. Enantioselective synthesis of (--)-gilbertine via a cationic cascade cyclization.

    PubMed

    Jiricek, Jan; Blechert, Siegfried

    2004-03-24

    Described is the first enantioselective synthesis of (-)-gilbertine (2), a member of the uleine-type family, and the determination of the absolute configuration of this natural product is reported. The key step employs a cationic cascade reaction for a tetrahydropyrane and piperidine ring formation and the construction of the pentacyclic framework in one step. The synthetic strategy utilizes the Shibasaki reaction to build up the first stereogenic center. A formylation reaction of a 3-substituted cyclohexanone derivative was achieved, giving only the desired regioisomer. The Japp-Klingemann Fischer indole protocol was used successfully as a convergent synthetic approach for the construction of the desired tetrahydrocarbazole (20). Furthermore, an unexpected behavior of this 2,3-disubstituted cyclohexanone derivative during an epimerization process was investigated, resulting in different chemical behavior of the enantiomers and the racemate. The diastereomeric resolution was achieved via the cationic cascade reaction, demonstrating the versatility of this approach. Significantly, the synthetic 17-step sequence was easy to execute, giving (-)-gilbertine in 5.5% overall yield.

  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. Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols.

    PubMed

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

    2016-04-21

    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.

  10. Enantioselective Synthesis of Chiral Piperidines via the Stepwise Dearomatization/Borylation of Pyridines.

    PubMed

    Kubota, Koji; Watanabe, Yuta; Hayama, Keiichi; Ito, Hajime

    2016-04-06

    We have developed a novel approach for the synthesis of enantioenriched 3-boryl-tetrahydropyridines via the Cu(I)-catalyzed regio-, diastereo-, and enantioselective protoborylation of 1,2-dihydropyridines, which were obtained by the partial reduction of the pyridine derivatives. This dearomatization/enantioselective borylation stepwise strategy provides facile access to chiral piperidines together with the stereospecific transformation of a stereogenic C-B bond from readily available starting materials. Furthermore, the utility of this method is demonstrated for the concise synthesis of the antidepressant drug (-)-paroxetine. A theoretical study of the reaction mechanism is also described.

  11. Enantioselective synthesis of α-quaternary Mannich adducts by palladium-catalyzed allylic alkylation: total synthesis of (+)-sibirinine.

    PubMed

    Numajiri, Yoshitaka; Pritchett, Beau P; Chiyoda, Koji; Stoltz, Brian M

    2015-01-28

    A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of "thermodynamic" enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N-H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine.

  12. Enantioselective synthesis of coumarin derivatives by PYBOX-DIPH-Zn(II) complex catalyzed Michael reaction.

    PubMed

    Ray, Sumit K; Singh, Pradeep K; Molleti, Nagaraju; Singh, Vinod K

    2012-10-05

    A potential pharmacologically active chiral 3-substituted 4-hydroxy-2-oxo-2H-chromene skeleton has been synthesized by enantioselective Michael addition catalyzed by PYBOX-DIPH-Zn(OTf)(2) complex. The methodology has successfully been employed in the synthesis of (R)-Warfarin and another related compounds.

  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. Enantioselective synthesis of Amaryllidaceae alkaloids (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine.

    PubMed

    Wei, Meng-Xue; Wang, Cheng-Tao; Du, Ji-Yuan; Qu, Hu; Yin, Pei-Rong; Bao, Xu; Ma, Xiao-Yan; Zhao, Xian-He; Zhang, Guo-Biao; Fan, Chun-An

    2013-09-01

    Cat. on a hot tin roof: Enantioselective catalytic Michael addition of α-cyanoketones to acrylates under bifunctional organocatalysis was used to construct the unique arylic all-carbon quaternary stereocenter, which is synthetically crucial in the chemical synthesis of optically pure cis-aryl hydroindole alkaloids. The protocol offers an asymmetric route to (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine.

  15. Enantioselective synthesis of planar-chiral benzosiloloferrocenes by Rh-catalyzed intramolecular C-H silylation.

    PubMed

    Shibata, Takanori; Shizuno, Tsubasa; Sasaki, Tomoya

    2015-05-07

    The first synthesis of planar-chiral benzosiloloferrocenes was achieved by the intramolecular reaction of 2-(dimethylhydrosilyl)arylferrocenes. The enantioselective cross dehydrogenative coupling of an sp(2) C-H bond of ferrocene with a Si-H bond proceeded efficiently with the use of a Rh-chiral diene catalyst.

  16. Organocatalyzed enantioselective synthesis of 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles

    PubMed Central

    Gogoi, Sanjib; Zhao, Cong-Gui

    2009-01-01

    The first enantioselective synthesis of biologically active 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles has been achieved through a cinchona alkaloid-catalyzed tandem Michael addition and Thorpe-Ziegler type reaction between 2-pyrazolin-5-ones and benzylidenemalononitriles. The reaction may also be carried out in a three-component or a four-component fashion via the in situ formation of these two components from simple and readily available starting materials. The desired products were obtained in excellent yields with mediocre to excellent enantioselectivities (up to >99% ee). PMID:19915654

  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 5-epi-citreoviral using ruthenium-catalyzed asymmetric ring-closing metathesis.

    PubMed

    Funk, Timothy W

    2009-11-05

    Chiral ruthenium olefin metathesis catalysts can perform asymmetric ring-closing reactions in > or = 90% ee with low catalyst loadings. To illustrate the practicality of these reactions and the products they form, an enantioselective total synthesis of 5-epi-citreoviral was completed by using an asymmetric ring-closing olefin metathesis reaction as a key step early in the synthesis. All of the stereocenters in the final compound were set by using the chiral center generated by asymmetric olefin metathesis.

  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.

  20. Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir.

    PubMed

    Thieme, Niels; Breit, Bernhard

    2017-02-01

    The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir.

  1. Enantioselective formal synthesis of uleine alkaloids from phenylglycinol-derived bicyclic lactams.

    PubMed

    Amat, Mercedes; Pérez, Maria; Llor, Núria; Martinelli, Marisa; Molins, Elies; Bosch, Joan

    2004-07-21

    A two-step route for the enantioselective construction of the tetracyclic ring system of uleine alkaloids, involving the stereoselective conjugate addition of an appropriate indole-containing nucleophile to a chiral bicyclic delta-lactam and the subsequent cyclization on the indole 3-position of the resulting 4,5-disubstituted 2-piperidone, has culminated in the formal total synthesis of several alkaloids of this group.

  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. 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

  4. Conjugate additions to phenylglycinol-derived unsaturated delta-lactams. Enantioselective synthesis of uleine alkaloids.

    PubMed

    Amat, Mercedes; Pérez, Maria; Llor, Núria; Escolano, Carmen; Luque, F Javier; Molins, Elies; Bosch, Joan

    2004-12-10

    The stereochemical outcome of the conjugate addition of a variety of stabilized nucleophiles (2-indoleacetic enolates and sulfur-stabilized anions) to the phenylglycinol-derived unsaturated lactams trans-2, cis-2, and its 8-ethyl-substituted analogue 10 is studied. The factors governing the exo or endo facial stereoselectivity are discussed. This methodology provides short synthetic routes to either cis- or trans-3,4-disubstituted enantiopure piperidines as well as efficient routes for the enantioselective construction of the tetracyclic ring system of uleine alkaloids, both in the normal and 20-epi series. The formal total synthesis of several alkaloids of this group is reported.

  5. Organocatalytic Enantioselective Synthesis of α-Hydroxyketones through a Friedel-Crafts Reaction of Naphthols and Activated Phenols with Aryl- and Alkylglyoxal Hydrates.

    PubMed

    Vila, Carlos; Quintero, Lucia; Blay, Gonzalo; Muñoz, M Carmen; Pedro, José R

    2016-11-04

    An efficient organocatalytic asymmetric synthesis of α-hydroxyketones has been developed. Quinine-derived thiourea catalyzed the enantioselective Friedel-Crafts alkylation of naphthols and activated phenols with aryl- and alkylglyoxal hydrates, providing the corresponding chiral α-hydroxyketones with high yields (up to 97%) and excellent enantioselectivities (up to 99% ee).

  6. Enantioselective synthesis of a chiral coordination polymer with circularly polarized visible laser.

    PubMed

    Wu, Shu-Ting; Cai, Zhen-Wen; Ye, Qiao-Yan; Weng, Chen-Hao; Huang, Xi-He; Hu, Xiao-Lin; Huang, Chang-Cang; Zhuang, Nai-Feng

    2014-11-17

    Circular dichroism is known to be the feature of a chiral agent which has inspired scientist to study the interesting phenomena of circularly polarized light (CPL) modulated molecular chirality. Although several organic molecules or assemblies have been found to be CPL-responsive, the influence of CPL on the assembly of chiral coordination compounds remains unknown. Herein, a chiral coordination polymer, which is constructed from achiral agents, was used to study the CPL-induced enantioselective synthesis. By irradiation with either left-handed or right-handed CPL during the reaction and crystallization, enantiomeric excesses of the crystalline product were obtained. Left-handed CPL resulted in crystals with a left-handed helical structure, and right-handed CPL led to crystals with a right-handed helical structure. It is exciting that the absolute asymmetric synthesis of a chiral coordination polymer could be enantioselective when using CPL, and provides a strategy for the control of the chirality of chiral coordination polymers.

  7. Enantioselective synthesis of planar chiral ferrocenes via Pd(0)-catalyzed intramolecular direct C-H bond arylation.

    PubMed

    Gao, De-Wei; Yin, Qin; Gu, Qing; You, Shu-Li

    2014-04-02

    A highly efficient synthesis of planar chiral ferrocenes by enantioselective Pd(0)-catalyzed direct C-H arylation from readily available starting materials under mild reaction conditions was developed (up to 99% yield, 99% ee). The products can be easily transformed to the highly efficient planar ferrocene ligands, which have demonstrated high efficiency in Pd-catalyzed asymmetric allylic alkylation and amination reactions.

  8. Enantioselective synthesis of (R)-tolterodine using lithiation/borylation–protodeboronation methodology

    PubMed Central

    Roesner, Stefan; Aggarwal, Varinder K.

    2013-01-01

    The synthesis of the pharmaceutical (R)-tolterodine is reported using lithiation/borylation–protodeboronation of a homoallyl carbamate as the key step. This step was tested with two permutations: an electron-neutral aryl Li-carbamate reacting with an electron-rich boronic ester and an electron-rich aryl Li-carbamate reacting with an electron-neutral boronic ester. It was found that the latter arrangement was considerably better than the former. Further improvements were achieved using magnesium bromide in methanol leading to a process that gave high yield and high enantioselectivity in the lithiation/borylation reaction. The key step was used in an efficient synthesis of (R)-tolterodine in a total of eight steps in a 30% overall yield and 90% ee. PMID:23750041

  9. 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

  10. 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.

  11. 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.

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

    PubMed

    Beaud, Rodolphe; Phipps, Robert J; Gaunt, Matthew J

    2016-10-12

    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.

  13. 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

  14. Asymmetric Friedel-Crafts alkylations of indoles with dialkyl 3-oxoprop-1-enylphosphonates: organocatalytic enantioselective synthesis of alpha-indolyl phosphonates.

    PubMed

    Guo, Ying-Cen; Li, Dong-Ping; Li, Yu-Ling; Wang, Hong-Mei; Xiao, Wen-Jing

    2009-08-01

    Organocatalytic enantioselective synthesis of alpha-indolyl phosphonates has been successfully carried out via asymmetric Friedel-Crafts alkylation of substituted indoles with (E)-dialkyl 3-oxoprop-1-enylphosphonates in 48-82% yield and 73-96% ee.

  15. 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

  16. 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.

  17. Enantioselective Cyclopropanation with α-Alkyl-α-diazoesters Catalyzed by Chiral Oxazaborolidinium Ion: Total Synthesis of (+)-Hamavellone B.

    PubMed

    Shim, Su Yong; Kim, Jae Yeon; Nam, Miso; Hwang, Geum-Sook; Ryu, Do Hyun

    2016-01-15

    Chiral oxazaborolidinium ion-catalyzed asymmetric cyclopropanation of α- or α,β-substituted acroleins with α-alkyl-α-diazoesters has been developed. With this methodology, chiral functionalized cyclopropanes containing a quaternary stereogenic center were obtained with high to excellent enantioselectivities (up to >99% ee). The synthetic utility of optically enriched functionalized cyclopropane was demonstrated in the first total synthesis of (+)-hamavellone B, which establishes the absolute configuration of natural (+)-hamavellone B.

  18. Enantioselective synthesis of AG-041R by using N-heteroarenesulfonyl cinchona alkaloid amides as organocatalysts.

    PubMed

    Hara, Noriyuki; Nakamura, Shuichi; Sano, Masahide; Tamura, Ryota; Funahashi, Yasuhiro; Shibata, Norio

    2012-07-23

    The organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to ketimines derived from isatins by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. The products could be converted into optically active AG-041R. X-ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8-quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.

  19. 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.

  20. Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes.

    PubMed

    Shi, Yan-Chao; Yang, Rong-Fei; Gao, De-Wei; You, Shu-Li

    2013-01-01

    When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent enantioselectivity (up to 99% ee).

  1. Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes

    PubMed Central

    Shi, Yan-Chao; Yang, Rong-Fei; Gao, De-Wei

    2013-01-01

    Summary When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent enantioselectivity (up to 99% ee). PMID:24062858

  2. Cu(I)/bis(azaferrocene)-catalyzed enantioselective synthesis of beta-lactams via couplings of alkynes with nitrones.

    PubMed

    Lo, Michael M-C; Fu, Gregory C

    2002-05-01

    As a consequence of the wide-ranging significance of beta-lactams (e.g., use as drugs and as chiral building blocks), a great deal of effort has been dedicated to the development of methods for their stereoselective synthesis. Although considerable progress has been achieved, nearly all of the approaches that have been described are based on the use of chiral precursors; direct catalytic enantioselective routes to beta-lactams are rare as well as limited in scope. In this communication, we establish that, using a new C2-symmetric planar-chiral bis(azaferrocene) ligand, we can generate beta-lactams with very good enantiomeric excess and cis diastereoselection via catalytic enantioselective Kinugasa reactions (couplings of alkynes with nitrones). Appealing attributes of this process include the ready availability of the starting materials, the functional-group tolerance of the reaction, and the convergency of the approach.

  3. Synthesis and studies of polypeptide materials: Enantioselective polymerization of gamma-benzyl glutamate-N-carboxyanhydride and synthesis of optically active poly(beta-peptides)

    NASA Astrophysics Data System (ADS)

    Cheng, Jianjun

    A class of zero-valent transition metal complexes have been developed by Deming et al for the controlled polymerization of alpha-aminoacid-N-carboxyanhydrides (alpha-NCAs). This discovery provided a superior starting point for the development of enantioselective polymerizations of racemic alpha-NCAs. Bidentate chiral ligands were synthesized and tested for their abilities to induce enantioselective polymerization of gamma-benzyl-glutamate NCA (Glu NCA) when they were coordinated to zero-valent nickel complexes. When optically active 2-pyridinyl oxazoline ligands were mixed with bis(1,5-cyclooctadiene)nickel in THF, chiral nickel complexes were formed that selectively polymerized one enantiomer of Glu NCA over the other. The highest selectivity was observed with the nickel complex of (S)-4-tert-butyl-2-pyridinyl oxazoline, which gave a ratio of enantiomeric polymerization rate constants (kD/kL) of 5.2. It was found that subtle modification of this ligand by incorporation of additional substituents had a substantial impact on initiator enantioselectivities. In separate efforts, methodology was developed for the general synthesis of optically active beta-aminoacid-N-carboxyanhydrides (beta-NCAs) via cyclization of Nbeta-Boc- or Nbeta-Cbz-beta-amino acids using phosphorus tribromide. The beta-NCA molecules could be polymerized in good yields using strong bases or transition metal complexes to give optically active poly(beta-peptides) bearing proteinogenic side chains. The resulting poly(beta-peptides), which have moderate molecular weights, adopt stable helical conformations in solution. Poly(beta-homoglutamate and poly(beta-homolysine), the side-chain deprotected polymers, were found to display pH dependent helix-coil conformation transitions in aqueous solution, similar to their alpha-analogs. A novel method for poly(beta-aspartate) synthesis was developed via the polymerization of L-aspartate alkyl ester beta lactams using metal-amido complexes. Poly

  4. 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

  5. Enantioselective synthesis of allenamides via sulfimide [2,3]-sigmatropic rearrangement.

    PubMed

    Armstrong, Alan; Emmerson, Daniel P G

    2009-04-02

    Chiral allenamides are prepared with high levels of enantiomeric purity by [2,3]-sigmatropic rearrangement of propargylic sulfimides. The required branched propargylic sulfides are prepared by an enantioselective organocatalytic aldehyde alpha-sulfenylation followed by Corey-Fuchs alkynylation.

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

    PubMed

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

    2016-08-05

    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.

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

    PubMed

    Li, Shen; Ma, Jun-An

    2015-11-07

    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.

  8. 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.

  9. Rh-Mediated Enantioselective Synthesis, Crystal Structures, and Photophysical/Chiroptical Properties of Phenanthrenol-Based [9]Helicene-like Molecules.

    PubMed

    Yamano, Ryota; Hara, Jun; Murayama, Koichi; Sugiyama, Haruki; Teraoka, Kota; Uekusa, Hidehiro; Kawauchi, Susumu; Shibata, Yu; Tanaka, Ken

    2017-01-06

    The enantioselective synthesis of phenanthrenol-based [9]helicene-like molecules has been achieved via the rhodium-mediated intramolecular [2 + 2 + 2] cycloadditions of 3-phenanthrenol-linked triynes. Crystal structures and photophysical/chiroptical properties of these [9]helicene-like molecules were compared with the corresponding [7]helicene-like molecules.

  10. Effect of high pressure on the organocatalytic asymmetric Michael reaction: highly enantioselective synthesis of γ-nitroketones with quaternary stereogenic centers.

    PubMed

    Kwiatkowski, Piotr; Dudziński, Krzysztof; Łyżwa, Dawid

    2011-07-15

    The significant effect of hydrostatic pressure on the difficult organocatalytic 1,4-conjugate addition of nitroalkanes to prochiral sterically congested β,β-disubstituted enones is demonstrated. This approach allows for the synthesis of γ-nitroketones containing quaternary stereogenic centers with good yields, excellent enantioselectivity, and low loading (1-5 mol %) of simple chiral primary amine catalysts.

  11. Enantioselective Synthesis of Anti-β-Substituted γ,δ-Unsaturated Amino Acids: A Highly Selective Asymmetric Thio-Claisen Rearrangement

    PubMed Central

    Liu, Zhihua; Qu, Hongchang; Gu, Xuyuan; Min, Byoung J.; Nyberg, Joel; Hruby, Victor J.

    2009-01-01

    A novel synthesis of optically active anti-1β-substituted γ,δ-unsaturated amino acids via a thio-Claisen rearrangement has been achieved. A 2,5-diphenylpyrrolidine was used as a C2-symmetric chiral auxiliary to control the stereochemistry, giving good yields and excellent diastereoselectivities and enantioselectivities. PMID:18702500

  12. Co(III)(salen)-catalyzed HKR of two stereocentered alkoxy- and azido epoxides: a concise enantioselective synthesis of (S,S)-reboxetine and (+)-epi-cytoxazone.

    PubMed

    Reddy, R Santhosh; Chouthaiwale, Pandurang V; Suryavanshi, Gurunath; Chavan, Vilas B; Sudalai, Arumugam

    2010-07-21

    The HKR of racemic syn- or anti- alkoxy- and azido epoxides catalyzed by Co(salen) complex affords a practical access to a series of enantioenriched syn- or anti- alkoxy- and azido epoxides and the corresponding 1,2-diols. This strategy has been successfully employed in the concise, enantioselective synthesis of bioactive molecules such as (S,S)-reboxetine and (+)-epi-cytoxazone.

  13. N-Heterocyclic Carbene-Catalyzed [4 + 2] Cyclization of Saturated Carboxylic Acid with o-Quinone Methides through in Situ Activation: Enantioselective Synthesis of Dihydrocoumarins.

    PubMed

    Wang, Yuanfeng; Pan, Jian; Dong, Jingjiao; Yu, Chenxia; Li, Tuanjie; Wang, Xiang-Shan; Shen, Shide; Yao, Changsheng

    2017-02-03

    An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] synthesis of dihydrocoumarins was realized from saturated carboxylic acids and o-quinone methides via an in situ activation strategy. This protocol results in excellent diastereoselectivity and enantioselectivity and good yields and uses readily available and inexpensive starting materials.

  14. An efficient and highly stereoselective synthesis of new P-chiral 1,5-diphosphanylferrocene ligands and their use in enantioselective hydrogenation.

    PubMed

    Chen, Weiping; Roberts, J Stanley M; Whittall, John; Steiner, Alexander

    2006-07-21

    An efficient and highly stereoselective synthesis of P-chiral 1,5-diphosphanylferrocene ligands has been developed, and the introduction of P-chirality in ferrocene-based phosphine ligands enhances the enantioselective discrimination produced by the corresponding catalyst when matching of the planar chirality, the chirality at carbon and the chirality at phosphorus occurs.

  15. Enantioselective Synthesis of α-Mercapto-β-amino Esters via Rh(II)/Chiral Phosphoric Acid-Cocatalyzed Three-Component Reaction of Diazo Compounds, Thiols, and Imines.

    PubMed

    Xiao, Guolan; Ma, Chaoqun; Xing, Dong; Hu, Wenhao

    2016-12-02

    An enantioselective method for the synthesis of α-mercapto-β-amino esters has been developed via a rhodium(II)/chiral phosphoric acid-cocatalyzed three-component reaction of diazo compounds, thiols, and imines. This transformation is proposed to proceed through enantioselective trapping of the sulfonium ylide intermediate generated in situ from the diazo compound and thiol by the phosphoric acid-activated imine. With this method, a series of α-mercapto-β-amino esters were obtained in good yields with moderate to good stereoselectivities.

  16. 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

  17. 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.

  18. Total Synthesis of Cryptocaryol A by Enantioselective Iridium-Catalyzed Alcohol C-H Allylation.

    PubMed

    Perez, Felix; Waldeck, Andrew R; Krische, Michael J

    2016-04-11

    The polyketide natural product cryptocaryol A is prepared in 8 steps via iridium catalyzed enantioselective diol double C-H allylation, which directly generates an acetate-based triketide stereodiad. In 4 previously reported total syntheses, 17-28 steps were required.

  19. Enantioselective synthesis of β-substituted chiral allylic amines via Rh-catalyzed asymmetric hydrogenation.

    PubMed

    Wang, Qingli; Gao, Wenchao; Lv, Hui; Zhang, Xumu

    2016-09-27

    An asymmetric mono-hydrogenation of 2-acetamido-1,3-dienes catalyzed by a Rh-DuanPhos complex has been developed. This approach provides easy access to chiral allylic amines with excellent enantioselectivities and high regioselectivities. The products are valuable chiral building blocks for pharmaceuticals.

  20. Enantioselective Synthesis of (+)-Estrone Exploiting a Hydrogen Bond-Promoted Diels−Alder Reaction

    PubMed Central

    2010-01-01

    Starting from Dane’s diene and methylcyclopentenedione, (+)-estrone is synthesized along the Quinkert−Dane route in 24% total yield. The key step is an enantioselective Diels−Alder reaction promoted by an amidinium catalyst as efficiently as by a traditional Ti-TADDOLate Lewis acid. PMID:20302330

  1. Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed direct coupling with arylboronic acids.

    PubMed

    Gao, De-Wei; Shi, Yan-Chao; Gu, Qing; Zhao, Zheng-Le; You, Shu-Li

    2013-01-09

    Enantioselective Pd(II)-catalyzed direct coupling of aminomethylferrocene derivatives with boronic acids was realized. With commercially available Boc-L-Val-OH as a ligand, planar-chiral ferrocenes could be synthesized in yields of 14-81% with up to 99% ee under mild conditions.

  2. Enantioselective sp(3) C-H alkylation of γ-butyrolactam by a chiral Ir(I) catalyst for the synthesis of 4-substituted γ-amino acids.

    PubMed

    Tahara, Yu-ki; Michino, Masamichi; Ito, Mamoru; Kanyiva, Kyalo Stephen; Shibata, Takanori

    2015-12-04

    Ir-catalyzed sp(3) C-H alkylation of γ-butyrolactam with alkenes was used for the highly enantioselective synthesis of 5-substituted γ-lactams, which were readily converted into chiral 4-substituted γ-amino acids. A broad scope of alkenes was amenable as coupling partners, and the alkylated product using acrylate could be transformed into the key intermediate of pyrrolam A synthesis.

  3. 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.

  4. Enantioselective Synthesis of β-(3-Hydroxypyrazol-1-yl)ketones Using An Organocatalyzed Michael Addition Reaction

    PubMed Central

    Gogoi, Sanjib; Zhao, Cong-Gui; Ding, Derong

    2009-01-01

    β-(3-Hydroxypyrazol-1-yl)ketones have been prepared in high yields and excellent enantioselectivities (94–98% ee) via a Michael addition reaction between 2-pyrazolin-5-ones and aliphatic acyclic α,β-unsaturated ketones using 9-epi-9-amino-9-deoxyquinine as the catalyst. These results account for the first example of an aza-Michael addition of the ambident 2-pyrazolin-5-one anion to a Michael acceptor. PMID:19415906

  5. 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

  6. Enantioselective synthesis of cyclic sulfamidates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation.

    PubMed

    Kang, Soyeong; Han, Juae; Lee, Eun Sil; Choi, Eun Bok; Lee, Hyeon-Kyu

    2010-09-17

    Asymmetric transfer hydrogenation (ATH) of cyclic sulfamidate imines 4 and 9, using a HCO(2)H/Et(3)N mixture as the hydrogen source and well-defined chiral Rh catalysts (S,S)- or (R,R)-2, Cp*RhCl(TsDPEN), effectively produces the corresponding cyclic sulfamidates with excellent yields and enantioselectivities at room temperature within 0.5 h. ATH of 4,5-disubstituted imines 9, having preexisting stereogenic centers, is shown to take place with dynamic kinetic resolution.

  7. 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.

  8. Brønsted Acid Catalyzed Addition of Enamides to ortho-Quinone Methide Imines-An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines.

    PubMed

    Kretzschmar, Martin; Hodík, Tomáš; Schneider, Christoph

    2016-08-08

    The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho-quinone methide imines and subsequent elimination. This novel one-step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N-heterocycles with a 1,4-dihydroquinoline motif. By subsequent highly diastereoselective hydrogenation and N-deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers.

  9. 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

  10. Organocatalytic, Enantioselective Synthesis of Cyclohexadienone Containing Hindered Spirocyclic Ethers through an Oxidative Dearomatization/Oxa-Michael Addition Sequence.

    PubMed

    Reddy, Reddy Rajasekhar; Gudup, Satish Sonbarao; Ghorai, Prasanta

    2016-11-21

    An unprecedented enantioselective oxa-Michael reaction of α-tertiary alcohols using cinchona-alkaloid-based chiral bifunctional squaramide catalysts is reported. An oxidative dearomatization of phenol followed by an enantioselective oxa-Michael addition sequence provided a broad array of chiral sterically hindered tetrahydrofurans and tetrahydropyrans attached to a cyclohexadienone moiety in spiro fashion. In general, good yields and excellent enantioselectivities (up to 99 %) were observed. The chiral oxo-cycles obtained have easily been transformed into chromans without disturbing the enantioselectivity.

  11. Enantioselective disposition of (R)-salmeterol and (S)-salmeterol in urine following inhaled dosing and application to doping control.

    PubMed

    Jacobson, Glenn A; Hostrup, Morten; Narkowicz, Christian K; Nichols, David S; Haydn Walters, E

    2016-11-07

    Salmeterol (USAN, INN, BAN) is a long-acting beta2-adrenoceptor agonist (LABA) widely used in the treatment of airways disease. Although salmeterol is permitted via inhalation by athletes and supratherapeutic dosing may enhance performance, no urine threshold has been established by the World Anti-Doping Agency (WADA). Salmeterol is a chiral compound consisting of (R)- and (S)-enantiomers, normally administered as racemic (rac-) mixture via inhalation. Levels of rac-salmeterol in urine are often below detectable levels and there is surprisingly little information regarding the enantioselectivity of salmeterol pharmacokinetics. In this study, subjects inhaled either 50 (n = 6) or 200 µg (n = 4; generally regarded as maximum therapeutic dose) of salmeterol and urine was then collected for 24 h and analyzed by enantioselective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Maximum rac-salmeterol urine concentrations were obtained at 2 h for both doses with medians of 0.084 ng/mL after the 50 µg dose and 2.1 ng/mL after the 200 µg dose, with an individual maximum of 5.7 ng/mL. Levels were detectable at 24 h for both doses. Salmeterol displayed enantioselective pharmacokinetics, with a mean ± SD log (S):(R) = 0.055 ± 0.025 (P < 0.0001) equivalent to (S):(R) of 1.13. In conclusion, rac-salmeterol by inhalation exhibits modest enantioselectivity in urine following single dose administration and can be detected following a single 50 µg dose for up to 24 h after inhalation. The present findings are of relevance if a urine threshold limit is to be introduced for salmeterol on the list of prohibited substances. The application of an enantiomer ratio analysis may offer improved discriminatory detection capability for doping control analysis applications.

  12. Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines.

    PubMed

    Amat, Mercedes; Semak, Vladislav; Escolano, Carmen; Molins, Elies; Bosch, Joan

    2012-09-14

    A practical enantioselective protecting group-free four-step route to the key quinolizidinone 6 from phenylglycinol-derived bicyclic lactam 1 is reported. The Grignard addition reaction to 6 takes place stereoselectively to give 1-ethyl-4-substituted quinolizidines 4-epi-207I and 7-9. Following a similar synthetic sequence, 9a-epi-6 is also accessed. However, the addition of Grignard reagents to 9a-epi-6 proceeds in a non-stereoselective manner. In order to gain insight into the different stereochemical outcome in the two series, theoretical calculations on the iminium salts A and B have been performed. The study concludes that the addition of the hydride, which is the step that determines the configuration of the final products, occurs in a stereoelectronic controlled manner. The theoretical study is in agreement with the experimental results.

  13. 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

  14. Enantioselective N-heterocyclic carbene-catalyzed synthesis of saccharine-derived dihydropyridinones with cis-selectivity.

    PubMed

    Liang, Zhi-Qin; Wang, Dong-Ling; Zhang, Chun-Lin; Ye, Song

    2016-07-06

    The enantioselective N-heterocyclic carbene-catalyzed [2 + 4] cyclocondensation of α-chloroaldehydes and saccharine-derived 1-azadienes was developed, giving the corresponding saccharine-derived dihydropyridinones in good yields with exclusive cis-selectivities and excellent enantioselectivities.

  15. Organocatalytic Enantioselective Synthesis of Tetrahydrofluoren-9-ones via Vinylogous Michael Addition/Henry Reaction Cascade of 1,3-Indandione-Derived Pronucleophiles.

    PubMed

    Möhlmann, Lennart; Chang, Geng-Hua; Madhusudhan Reddy, G; Lee, Chia-Jui; Lin, Wenwei

    2016-02-19

    An unprecedented organocatalytic enantioselective vinylogous Michael addition/Henry cyclization cascade is presented for the synthesis of highly substituted tetrahydrofluoren-9-ones 3 employing novel 1,3-indandione-derived pronucleophiles 1a-g and nitroalkenes 2. Following a very simple protocol, a wide range of products were obtained in good to excellent yields and with excellent enantioinduction (43-98% yield, up to 98% ee). The reaction proceeded with excellent diastereocontrol despite the simultaneous generation of four stereogenic centers. Surprisingly, when 2-(1-phenylethylidene)-1H-indandione (1h) was used as a pronucleophile, no cyclization was observed, and only Michael addition adducts 4a-x were furnished in very good yields and excellent enantioselectivities.

  16. Enantioselective synthesis of spiro γ-butyrolactones by N-heterocyclic carbene (NHC)-catalyzed formal [3 + 2] annulation of enals with 3-hydroxy oxindoles.

    PubMed

    Mukherjee, Subrata; Joseph, Sumi; Bhunia, Anup; Gonnade, Rajesh G; Yetra, Santhivardhana Reddy; Biju, Akkattu T

    2017-02-15

    The N-heterocyclic carbene (NHC)-catalyzed enantioselective formal [3 + 2] annulation of α,β-unsaturated aldehydes with 3-hydroxy oxindoles is presented. Under oxidative conditions using the bisquinone oxidant, the reaction resulted in the synthesis of spiro γ-butyrolactones in moderate to good yields, enantioselectivity and diastereoselectivity. The reaction likely proceeds via the generation of the NHC-bound α,β-unsaturated acylazolium intermediate from enals, which was intercepted by the dioxindoles in a formal [3 + 2] pathway to form the spirocyclic compounds. However, a deeper mechanistic investigation revealed that the reaction can also proceed via the homoenolate intermediate. In this case, the dioxindole was oxidized to the corresponding isatin derivative using traces of air under basic conditions, and was intercepted with the NHC-bound homoenolate intermediate in a formal [3 + 2] pathway to afford the spiro compound.

  17. Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies

    PubMed Central

    2015-01-01

    The catalytic asymmetric synthesis of alkyl fluorides, particularly α-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C6F5ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C6F5ONa) is critical for turnover, releasing the catalyst (PPY*) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an α-fluoro-N-acylpyridinium salt, have been examined. PMID:24922581

  18. Copper(I)-catalyzed enantioselective synthesis of α-chiral linear or carbocyclic (E)-(γ-alkoxyallyl)boronates.

    PubMed

    Yamamoto, Eiji; Takenouchi, Yuta; Ozaki, Taichi; Miya, Takanori; Ito, Hajime

    2014-11-26

    A new method has been developed for the catalytic asymmetric synthesis of α-chiral linear or carbocyclic (γ-alkoxyallyl)boronates via the copper(I)-catalyzed γ-boryl substitution of allyl acetals. This reaction afforded the products in high yields with excellent E:Z selectivities and enantioselectivities [only (E)-product, 91-98% ee] and also exhibited high functional group compatibility. Subsequent allylation of aldehydes with the α-chiral (γ-alkoxyallyl)boronates provided the anti-1,2-diol derivatives in a highly stereospecific manner, and the utility of the α-chiral (γ-alkoxyallyl)boronates was further demonstrated by a convergent coupling of a complex polyol derivative using a (γ-alkoxyallyl)boronate and a chiral α-oxyaldehyde. The stereoselective modular construction of a complex 3,3-disubstituted cyclopentene containing three consecutive stereocenters including a quaternary chiral carbon was also reported. Useful transformations of the α-chiral linear (γ-alkoxyallyl)boronates were also demonstrated.

  19. Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.

    PubMed

    Xu, Shiqing; Oda, Akimichi; Negishi, Ei-ichi

    2014-12-01

    Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non-measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1-alkanols, with ≥99 % enantiomeric excess (ee), by the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu-catalyzed cross-coupling reactions. ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected ω-alkene-1-ols protocols were applied to the synthesis of both (R)- and (S)-difunctional intermediates with 80-90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1-alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium-labeled groups by Cu-catalyzed cross-coupling reactions without epimerization.

  20. Organocatalytic enantioselective direct additions of aldehydes to 4-vinylpyridines and electron-deficient vinylarenes and their synthetic applications.

    PubMed

    Wang, Sinan; Li, Xiangmin; Liu, Hongwei; Xu, Li; Zhuang, Jinchen; Li, Jian; Li, Hao; Wang, Wei

    2015-02-18

    We describe a synergistic catalysis strategy for the asymmetric direct addition of simple aldehydes to 4-vinylpyridines. By means of independent activation of weakly electrophilic 4-vinylpyridines by the Brønsted acid CF3SO3H (TfOH) and aldehydes by chiral diphenylprolinol tert-butyldimethylsilyl (TBDMS) ether-catalyzed formation of nucleophilic enamines in a cooperative manner, the previously unattainable highly enantioselective addition process has been realized for the first time. Notably, the power of the addition process is fueled by its high efficiency in the production of synthetically valued chiral pyridines. (1)H NMR studies of the process suggested that the nucleophilic enamine formed in situ from the chiral amine catalyst and the aldehyde is directly added to the trimeric 4-vinylpyridinium-derived species as a highly active electrophile generated from the 4-vinylpyridine in the presence of TfOH. Moreover, inspired by the similar electronic natures of pyridine and nitrobenzene, we have achieved an unprecedented chiral diphenylprolinol TBDMS ether-promoted, highly enantioselective direct addition of aldehydes to 2-nitrostyrenes without the use of TfOH as a cocatalyst. In this approach, introducing a strong electron-withdrawing group such as NO2, CF3, SO2Me, etc. on the 2-nitrostyrene creates a highly electrophilic vinyl moiety, which enables the direct addition of the in situ-formed enamine derived from the chiral amine promoter and the aldehyde. This method significantly expands the scope of the enantioselective addition process. While the electron-withdrawing nitro group is essential for activation of the vinyl group, we have demonstrated that it can be readily transformed to diverse functionalities. Furthermore, as shown, a chiral pyridine adduct serves as a key building block in the synthesis of the potent fibrinogen receptor antagonist L-734,217.

  1. 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

    2011-03-04

    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.

  2. Nickel-catalyzed enantioselective alkylative coupling of alkynes and aldehydes: synthesis of chiral allylic alcohols with tetrasubstituted olefins.

    PubMed

    Yang, Yun; Zhu, Shou-Fei; Zhou, Chang-Yue; Zhou, Qi-Lin

    2008-10-29

    A highly efficient nickel-catalyzed asymmetric alkylative coupling of alkynes, aldehydes, and dimethylzinc has been realized by using bulky spirobiindane phosphoramidite ligands, affording allylic alcohols with a tetrasubstituted olefin functionality in high yields, high regioselectivities, and excellent enantioselectivities.

  3. Asymmetric synthesis of planar chiral ferrocenes by enantioselective intramolecular C-H arylation of N-(2-haloaryl)ferrocenecarboxamides.

    PubMed

    Liu, Lantao; Zhang, An-An; Zhao, Rui-Juan; Li, Feng; Meng, Tuan-Jie; Ishida, Naoki; Murakami, Masahiro; Zhao, Wen-Xian

    2014-10-17

    The palladium-catalyzed intramolecular C-H arylation reaction of N-(2-bromoaryl)ferrocenecarboxamides furnishes planar chiral ferrocene derivatives. TADDOL-derived phosphoramide ligands induce enantioselectivities ranging from 91:9 to 98:2 er.

  4. Enantioselective gas chromatography/mass spectrometry of methylsulfonyl PCBs with application to arctic marine mammals.

    PubMed

    Wiberg, K; Letcher, R; Sandau, C; Duffe, J; Norstrom, R; Haglund, P; Bidleman, T

    1998-09-15

    Four different commercially available cyclodextrin (CD) capillary gas chromatography (GC) columns were tested for the enantioselective separation of nine environmentally persistent atropisomeric 3- and 4-methylsulfonyl PCBs (MeSO2-CBs). The selected columns contained cyclodextrins with various cavity diameters (beta- or gamma-CD), which were methylated and/or tert-butyldimethylsilylated (TBDMS) in the 2,3,6-O-positions. The beta-CD column with TBDMS substituents in all of the 2,3,6-O-positions was by far the most selective column for the MeSO2-CBs tested. Enantiomers of congeners with 3-MeSO2 substitution were more easily separated than those with 4-MeSO2 substitution. The separation also seemed to be enhanced for congeners with the chlorine atoms on the non-MeSO2-containing ring and clustered on one side of the same ring. The 2,3-di-O-methyl-6-O-TBDMS-beta-CD was found to give somewhat better selectivity than the corresponding gamma-CD, in comparison between the two columns, which were identical in all other respects. Enantioselective analysis of arctic ringed seal (Phoca hispida) and polar bear (Ursus maritimus) adipose tissue revealed a strong dominance of certain enantiomers. For example, the enantiomer ratio (ER) of 3-MeSO2-CB149 was 0.32 and < 0.1 in ringed seal blubber and polar bear fat, respectively. These low ER values are indicative of highly enantioselective formation, enantioselective metabolism, enantioselective transport across cell membranes, or a combination of the three in both species. Comparable results for the enantiomeric analysis of MeSO2-CBs in biotic tissue extracts were obtained using two highly selective mass spectrometric techniques, ion trap mass spectrometry/mass spectrometry and electron capture negative ion low-resolution mass spectrometry.

  5. Kinetic Resolution Driven Diastereo- and Enantioselective Synthesis of cis-β-Heteroaryl Amino Cycloalkanols by Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation.

    PubMed

    Vyas, Vijyesh K; Bhanage, Bhalchandra M

    2016-12-16

    The utility of tethered Ru-TsDPEN catalyst has been demonstrated for the asymmetric transfer hydrogenation of rac-α-heteroaryl amino cycloalkanones to construct biologically important cis-β-heteroaryl amino cycloalkanols with two contiguous chiral centers via dynamic kinetic resolution. The stated (R,R)-Teth-TsDPEN-Ru-catalyzed transformation is carried out under mild conditions using formic acid/triethylamine as a hydrogen source with excellent diastereo- and enantioselectivities. Further, this methodology has been applied for the synthesis of an antileishmanial agent and chiral ionic liquid.

  6. Enantioselective cyclopolymerization of 1,5-hexadiene catalyzed by chiral zirconocenes: A novel strategy for the synthesis of optically active polymers with chirality in the main chain

    SciTech Connect

    Coates, G.W.; Waymouth, R.M. )

    1993-01-13

    Enantioselective cyclopolymerization represents a novel strategy for the synthesis of optically active main-chain chiral polymers. Cyclopolymerization of 1,5-hexadiene using the optically active catalyst precursor, (R,R)-(EBTHI)ZrBINOL ((R,R)-1) [EBTHI = ethylene-1,2-bis([eta][sup 5]-4,5,6,7-tetrahydro-1-indenyl); BINOL = 1,1[prime]-bi-2-naphtholate], yields optically active poly(methylene-1,3-cyclopentane) (PMCP) with a molar optical rotation of [[Phi

  7. Enantioselective access to 2,7-cis-disubstituted oxepanes: formal synthesis of (+)-isolaurepan.

    PubMed

    Carreño, M Carmen; Des Mazery, Renaud; Urbano, Antonio; Colobert, Françoise; Solladié, Guy

    2004-01-22

    [reaction: see text] The asymmetric synthesis of 2,7-cis-disubstituted oxepanes bearing a sulfoxide is achieved from commercially available precursors in only five steps. The key step is the highly diastereoselective Et3SiH/TMSOTf-promoted reductive cyclization of enantiopure hydroxysulfinyl aryl or alkyl ketones.

  8. 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.

  9. Absolute asymmetric synthesis of enantiopure organozinc reagents, followed by highly enantioselective chlorination.

    PubMed

    Olsson, Susanne; Lennartson, Anders; Håkansson, Mikael

    2013-09-09

    We report the absolute asymmetric synthesis (AAS) of indenylzinc reagents by using total spontaneous resolution followed by enantiospecific conversion into 1-chloroindene. The chiral complex [Zn(dcp)(ind)(tmeda)] (dcp = 2,6-dichlorophenoxy and tmeda = N,N,N',N'-tetramethylethylenediamine) (3) was prepared from the achiral starting materials indene, potassium, zinc chloride, TMEDA, and 2,6-dichlorophenol. The reagent resolved spontaneously on crystallization, and single crystals of 3 react with N-chlorosuccinimide in the presence of benzoquinone in 2-propanol to give 1-chloroindene in >98 % enantiomeric excess. It was found that (R)-3 gave (R)-1-chloroindene upon reaction, indicating an SE 2'-mechanism. Since bulk samples of 3 gave optically active product upon chlorination, total spontaneous resolution must have occurred. This demonstrates that enantiopure products can be obtained through the absolute asymmetric synthesis of organometallic reagents starting from achiral materials. The general absolute asymmetric synthesis (AAS) method offers easy access to both enantiomers and an almost limitless variation in the design of the product.

  10. 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

  11. Highly enantioselective synthesis of beta-heteroaryl-substituted dihydrochalcones through Friedel-Crafts alkylation of indoles and pyrrole.

    PubMed

    Wang, Wentao; Liu, Xiaohua; Cao, Weidi; Wang, Jun; Lin, Lili; Feng, Xiaoming

    2010-02-01

    A highly enantioselective Friedel-Crafts (F-C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N'-dioxide-Sc(OTf)(3) complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85-92 % enantiomeric excess) using 2 mol % (for indole) or 0.5 mol % (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction.

  12. Recent advances on the enantioselective synthesis of C-nucleosides inhibitors of inosine monophosphate dehydrogenase (IMPDH).

    PubMed

    Merino, Pedro; Ghirardello, Mattia; Tejero, Tomas; Delso, Ignacio; Matute, Rosa

    2014-01-01

    This review will describe the recent advances in the synthesis of C-nucleosides with inhibitory activity of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the biosynthesis of guanine nucleotides. The review will cover synthetic approaches of structural analogues showing modifications in the furanose ring as well as in the heterocyclic base. Heterocyclic sugar nucleoside analogues in which the furanose ring has been replaced by a different heterocyclic ring including aza analogues, thioanalogues as well as dioxolanyl and isoxazolidinyl analogues are also considered.

  13. 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.

  14. Enantioselective synthesis of beta-aryl-gamma-amino acid derivatives via Cu-catalyzed asymmetric 1,4-reductions of gamma-phthalimido-substituted alpha,beta-unsaturated carboxylic acid esters.

    PubMed

    Deng, Jun; Hu, Xiang-Ping; Huang, Jia-Di; Yu, Sai-Bo; Wang, Dao-Yong; Duan, Zheng-Chao; Zheng, Zhuo

    2008-08-01

    A series of chiral beta-aryl-substituted gamma-amino butyric acid derivatives were synthesized in good enantioselectivities via the Cu-catalyzed asymmetric conjugate reduction of gamma-phthalimido-alpha,beta-unsaturated carboxylic acid esters using Cu(OAc)2 x H2O as a catalyst precursor, (S)-BINAP as a ligand, PMHS as a hydride source, and t-BuOH as an additive. The methodology has been applied successfully to the enantioselective synthesis of a chiral pharmaceutical, (R)-baclofen.

  15. Synthesis of highly functionalized chiral 3,3'-disubstituted oxindoles via an organocatalytic enantioselective Michael addition of nitroalkanes to indolylidenecyanoacetates.

    PubMed

    Liu, Lu; Wu, Deyan; Zheng, Shu; Li, Tengfei; Li, Xiangmin; Wang, Sinan; Li, Jian; Li, Hao; Wang, Wei

    2012-01-06

    An efficient bifunctional cinchona alkaloid derived thiourea-promoted enantioselective conjugate addition of nitroalkanes to indolylidenecyanoacetates has been developed under neat conditions. The process leads to synthetically interesting densely functionalized 3,3'-disubstituted oxindoles with creation of up to three stereogenic centers.

  16. An asymmetric alkynylation/hydrothiolation cascade: an enantioselective synthesis of thiazolidine-2-imines from imines, acetylenes and isothiocyanates.

    PubMed

    Ranjan, Alok; Mandal, Anupam; Yerande, Swapnil G; Dethe, Dattatraya H

    2015-09-28

    A multicomponent reaction between imines, terminal alkynes, and isothiocyanates in the presence of a catalytic chiral copper-pybox complex proceeds enantioselectively to give enantiopure thiazolidine-2-imines (60-99% ee) via a highly regioselective intramolecular 5-exo-dig hydrothiolation reaction.

  17. 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.

  18. 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

    2014-10-03

    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.

  19. Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis

    PubMed Central

    Noble, Adam; Roesner, Stefan

    2016-01-01

    Abstract Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly‐line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio‐ and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate‐controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps. PMID:27865037

  20. 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.

  1. 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

  2. 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.

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

    PubMed Central

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

    2016-01-01

    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 additions 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 synthesis of anti-parasitic drug Bravecto™ (presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in controlling enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate future development of transformations involving fluoro-organic entities. PMID:27442282

  4. Enantioselective Synthesis of Spiroindenes by Enol-Directed Rhodium(III)-Catalyzed C–H Functionalization and Spiroannulation

    PubMed Central

    Reddy Chidipudi, Suresh; Burns, David J; Khan, Imtiaz; Lam, Hon Wai

    2015-01-01

    Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp2)-H functionalization and oxidative annulation with alkynes to give spiroindenes containing all-carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O-bound rhodium enolate into the C-bound isomer, appear to be critical for high enantiomeric excesses. PMID:26404643

  5. Asymmetric synthesis of chiral dihydrothiopyrans via an organocatalytic enantioselective formal thio [3 + 3] cycloaddition reaction with binucleophilic bisketone thioethers.

    PubMed

    Wang, Shengzheng; Zhang, Yongqiang; Dong, Guoqiang; Wu, Shanchao; Zhu, Shiping; Miao, Zhenyuan; Yao, Jianzhong; Li, Hao; Li, Jian; Zhang, Wannian; Sheng, Chunquan; Wang, Wei

    2013-11-01

    An unprecedented organocatalytic highly enantioselective approach to a 3,4-dihydro-2H-thiopyran scaffold with two contiguous stereogenic centers has been implemented through a formal thio [3 + 3] cycloaddition process involving a Michael-aldol condensation cascade sequence. Notably, a new class of binucleophilic bisketone thioethers is designed for the process. Furthermore, the fine-tuning of their reactivity enables the cascade process to proceed with highly regioselectively.

  6. Ir-catalyzed allylic amination/ring-closing metathesis: a new route to enantioselective synthesis of cyclic beta-amino alcohol derivatives.

    PubMed

    Lee, Jun Hee; Shin, Seunghoon; Kang, Jahyo; Lee, Sang-gi

    2007-09-14

    Ir-catalyzed allylic aminations of (E)-4-benzyloxy-2-butenyl methyl carbonate with benzylamine using Feringa's (Sa,Sc,Sc)-phosphoramidite as a chiral ligand afforded linear-aminated achiral product N,O-dibenzyl-4-amino-2-buten-1-ol regioselectively (linear/branched = >99/1), whereas the (E)-5-benzyloxy-2-pentenyl methyl carbonate showed completely opposite regioselectivity (linear/branched = >1/99) and afforded the optically active (3R)-N,O-dibenzylated 3-amino-1-penten-5-ol with very high enantioselectivity (96% ee), which was used as a key intermediate for the effective synthesis of various cyclic beta-amino alcohol derivatives through ring-closing metathesis in high yields.

  7. 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.

  8. Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations: Application to Enantioselective Organocatalysis.

    PubMed

    Kamachi, Takashi; Yoshizawa, Kazunari

    2016-02-22

    A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost.

  9. 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.

  10. Chromium(II)-catalyzed enantioselective arylation of ketones

    PubMed Central

    Wang, Gang; Sun, Shutao; Mao, Ying; Xie, Zhiyu

    2016-01-01

    The chromium-catalyzed enantioselective addition of carbo halides to carbonyl compounds is an important transformation in organic synthesis. However, the corresponding catalytic enantioselective arylation of ketones has not been reported to date. Herein, we report the first Cr-catalyzed enantioselective addition of aryl halides to both arylaliphatic and aliphatic ketones with high enantioselectivity in an intramolecular version, providing facile access to enantiopure tetrahydronaphthalen-1-ols and 2,3-dihydro-1H-inden-1-ols containing a tertiary alcohol. PMID:28144349

  11. Organocatalytic, Diastereo- and Enantioselective Synthesis of Nonsymmetric cis-Stilbene Diamines: A Platform for the Preparation of Single-Enantiomer cis-Imidazolines for Protein–Protein Inhibition

    PubMed Central

    2015-01-01

    The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein–protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatographic separation using high-pressure liquid chromatography (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsymmetric cis-stilbene diamines and cis-imidazolines. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsymmetric cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate–catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chemical tools for disrupting protein–protein interactions. PMID:25017623

  12. Enantioselective synthesis of bicylco[3.2.1]octan-8-ones using a tandem Michael-Henry reaction

    PubMed Central

    Ding, Derong; Zhao, Cong-Gui; Guo, Qunsheng; Arman, Hadi

    2010-01-01

    Bicyclo[3.2.1]octan-8-ones have been prepared from a tandem Michael-Henry reaction between cyclohexane-1,2-diones and nitroalkenes using a quinine-derived thiourea as the catalyst. Although four stereogenic centers were created during the reaction, only two diastereomers were obtained in good diastereoselectivity and high enantioselectivity (92-99% ee). When 3-methylcyclohexane-1,2-dione (R1 = Me) was used as the substrate, only the regioisomeric product of the corresponding thermodynamic enolate was obtained. PMID:20532185

  13. 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.

  14. 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.

  15. 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

  16. Enantioselective imine reduction catalyzed by imine reductases and artificial metalloenzymes.

    PubMed

    Gamenara, Daniela; Domínguez de María, Pablo

    2014-05-21

    Adding value to organic synthesis. Novel imine reductases enable the enantioselective reduction of imines to afford optically active amines. Likewise, novel bioinspired artificial metalloenzymes can perform the same reaction as well. Emerging proof-of-concepts are herein discussed.

  17. Enantioselective Reduction of Ketones and Imines Catalyzed by (CN-Box)Re(V)-Oxo Complexes

    PubMed Central

    Nolin, Kristine A.; Ahn, Richard W.; Kobayashi, Yusuke; Kennedy-Smith, Joshua J.

    2012-01-01

    The development and application of chiral, non-racemic Re(V)-oxo complexes to the enantioselective reduction of prochiral ketones is described. In addition to the enantioselective reduction of prochiral ketones, we report the application of these complexes to (1) a tandem Meyer-Schuster rearrangement/reduction to access enantioenriched allylic alcohols and (2) the enantioselective reduction of imines. PMID:20623567

  18. S(N)2 reaction of sulfur nucleophiles with hindered sulfamidates: enantioselective synthesis of alpha-methylisocysteine.

    PubMed

    Avenoza, Alberto; Busto, Jesús H; Jiménez-Osés, Gonzalo; Peregrina, Jesús M

    2006-02-17

    The work described here demonstrates that the five-membered cyclic alpha-methylisoserine-derived sulfamidate, (R)-1, behaves as an excellent chiral building block for the ring-opening reaction by S(N)2 attack with sulfur nucleophiles at the quaternary carbon. As a synthetic application of this methodology, and to show that this sulfamidate is a valuable starting material, the synthesis of two new alpha-methylisocysteine derivatives has been carried out to cover the lack of alpha- and beta-methylated amino acids that incorporate the cysteine or isocysteine skeleton. These compounds are two new alpha,alpha-disubstituted beta-amino acids (beta(2,2)-amino acids), and the synthetic routes involve nucleophilic ring opening followed by acid hydrolysis.

  19. Crystal structure and characterization of esterase Est25 mutants reveal improved enantioselectivity toward (S)-ketoprofen ethyl ester.

    PubMed

    Kim, Jinyeong; Seok, Seung-Hyeon; Hong, Eunsoo; Yoo, Tae Hyeon; Seo, Min-Duk; Ryu, Yeonwoo

    2017-03-01

    Esterases comprise a group of enzymes that catalyze the cleavage and synthesis of ester bonds. They are important in biotechnological applications owing to their enantioselectivity, regioselectivity, broad substrate specificity, and the fact that they do not require cofactors. In a previous study, we isolated the esterase Est25 from a metagenomic library. Est25 showed catalytic activity toward the (R,S)-ketoprofen ethyl ester but had low enantioselectivity toward the (S)-ketoprofen ethyl ester. Because (S)-ketoprofen has stronger anti-inflammatory effects and fewer side effects than (R)-ketoprofen, enantioselectivity of this esterase is important. In this study, we generated Est25 mutants with improved enantioselectivity toward the (S)-ketoprofen ethyl ester; improved enantioselectivity of mutants was established by analysis of their crystal structures. The enantioselectivity of mutants was influenced by substitution of Phe72 and Leu255. Substituting these residues changed the size of the binding pocket and the entrance hole that leads to the active site. The enantioselectivity of Est25 (E = 1.1 ± 0.0) was improved in the mutants F72G (E = 1.9 ± 0.2), L255W (E = 16.1 ± 1.1), and F72G/L255W (E = 60.1 ± 0.5). Finally, characterization of Est25 mutants was performed by determining the optimum reaction conditions, thermostability, effect of additives, and substrate specificity after substituting Phe72 and Leu255.

  20. Organocatalyzed enantioselective protonation of silyl enol ethers: scope, limitations, and application to the preparation of enantioenriched homoisoflavones.

    PubMed

    Poisson, Thomas; Gembus, Vincent; Dalla, Vincent; Oudeyer, Sylvain; Levacher, Vincent

    2010-11-19

    In the present work, enantioselective protonation of silyl enol ethers is reported by means of a variety of chiral nitrogen bases as catalysts, mainly derived from cinchona alkaloids, in the presence of various protic nucleophiles as proton source. A detailed study of the most relevant reaction parameters is disclosed allowing high enantioselectivities of up to 92% ee with excellent yields to be achieved under mild and eco-friendly conditions. The synthetic utility of this organocatalytic protonation was demonstrated during the preparation of two homoisoflavones 4a and 4b, isolated from Chlorophytum Inornatum and Scilla Nervosa, which were obtained with 81% and 78% ee, respectively.

  1. Enantioselective synthesis of α-phenyl- and α-(dimethylphenylsilyl)alkylboronic esters by ligand mediated stereoinductive reagent-controlled homologation using configurationally labile carbenoids.

    PubMed

    Barsamian, Adam L; Wu, Zhenhua; Blakemore, Paul R

    2015-03-28

    Chain extension of boronic esters by the action of configurationally labile racemic lithium carbenoids in the presence of scalemic bisoxazoline ligands was explored for the enantioselective synthesis of the two title product classes. Enantioenriched 2° carbinols generated by oxidative work-up (NaOOH) of initial α-phenylalkylboronate products were obtained in 35-83% yield and 70-96% ee by reaction of B-alkyl and B-aryl neopentyl glycol boronates with a combination of O-(α-lithiobenzyl)-N,N-diisopropylcarbamate and ligand 3,3-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl] pentane in toluene solvent (-78 °C to rt) with MgBr2·OEt2 additive. Enantioenriched α-(dimethylsilylphenylsilyl)alkylboronates were obtained in 35-69% yield and 9-57% ee by reaction of B-alkyl pinacol boronates with a combination of lithio(dimethylphenylsilyl)methyl 2,4,6-triisopropylbenzoate and ligand 2,2-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl]propane in cumene solvent (-45 °C to -95 °C to rt). The stereochemical outcome of the second type of reaction depended on the temperature history of the organolithium·ligand complex indicating that the stereoinduction mechanism in this case involves some aspect of dynamic thermodynamic resolution.

  2. Fast evaluation of enantioselective drug metabolism by electrophoretically mediated microanalysis: application to fluoxetine metabolism by CYP2D6.

    PubMed

    Asensi-Bernardi, Lucía; Martín-Biosca, Yolanda; Escuder-Gilabert, Laura; Sagrado, Salvador; Medina-Hernández, María José

    2013-12-01

    In this work, a capillary electrophoretic methodology for the enantioselective in vitro evaluation of drugs metabolism is applied to the evaluation of fluoxetine (FLX) metabolism by cytochrome 2D6 (CYP2D6). This methodology comprises the in-capillary enzymatic reaction and the chiral separation of FLX and its major metabolite, norfluoxetine enantiomers employing highly sulfated β-CD and the partial filling technique. The methodology employed in this work is a fast way to obtain a first approach of the enantioselective in vitro metabolism of racemic drugs, with the additional advantage of an extremely low consumption of enzymes, CDs and all the reagents involved in the process. Michaelis-Menten kinetic parameters (Km and Vmax ) for the metabolism of FLX enantiomers by CYP2D6 have been estimated by nonlinear fitting of experimental data to the Michaelis-Menten equation. Km values have been found to be 30 ± 3 μM for S-FLX and 39 ± 5 μM for R-FLX. Vmax estimations were 28.6 ± 1.2 and 34 ± 2 pmol·min(-1) ·(pmol CYP)(-1) for S- and R-FLX, respectively. Similar results were obtained using a single enantiomer (R-FLX), indicating that the use of the racemate is a good option for obtaining enantioselective estimations. The results obtained show a slight enantioselectivity in favor of R-FLX.

  3. Catalytic Enantioselective Synthesis of C 1‐ and C 2‐Symmetric Spirobiindanones through Counterion‐Directed Enolate C‐Acylation

    PubMed Central

    Rahemtulla, Benjamin F.; Clark, Hugh F.

    2016-01-01

    Abstract A catalytic enantioselective route to C1‐ and C2‐symmetric 2,2′‐spirobiindanones has been realized through an intramolecular enolate C‐acylation. This reaction employs a chiral ammonium counterion to direct the acylation of an in situ generated ketone enolate with a pentafluorophenyl ester. This reaction constitutes the first example of a direct catalytic enantioselective C‐acylation of a ketone and provides an efficient and highly enantioselective route to axially chiral spirobiindanediones. These products can be diastereoselectively derivatized, offering access to a range of functionalized spirocyclic architectures. PMID:27628946

  4. Highly enantioselective intramolecular 1,3-dipolar cycloaddition: a route to piperidino-pyrrolizidines.

    PubMed

    Vidadala, Srinivasa Rao; Golz, Christopher; Strohmann, Carsten; Daniliuc, Constantin-G; Waldmann, Herbert

    2015-01-07

    Enantioselective catalytic intermolecular 1,3-dipolar cycloadditions are powerful methods for the synthesis of heterocycles. In contrast, intramolecular enantioselective 1,3-dipolar cycloadditions are virtually unexplored. A highly enantioselective synthesis of natural-product-inspired pyrrolidino-piperidines by means of an intramolecular 1,3-dipolar cycloaddition with azomethine ylides is now reported. The method has a wide scope and yields the desired cycloadducts with four tertiary stereogenic centers with up to 99% ee. Combining the enantioselective catalytic intramolecular 1,3-dipolar cycloaddition with a subsequent diastereoselective intermolecular 1,3-dipolar cycloaddition yielded complex piperidino-pyrrolizidines with very high stereoselectivity in a one-pot tandem reaction.

  5. 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.

  6. Application of chiral mixed phosphorus/sulfur ligands to enantioselective rhodium-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation processes.

    PubMed

    Evans, David A; Michael, Forrest E; Tedrow, Jason S; Campos, Kevin R

    2003-03-26

    Chiral mixed phosphorus/sulfur ligands 1-3 have been shown to be effective in enantioselective Rh-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation reactions (eqs 1, 2). After assaying the influence of the substituents at sulfur, the substituents on the ligand backbone, the relative stereochemistry within the ligand backbone, and the substituents at phosphorus, ligands 2c (R = 3,5-dimethylphenyl) and 3 were found to be optimal in the Rh-catalyzed hydrogenation of a variety of alpha-acylaminoacrylates in high enantioselectivity (89-97% ee). A similar optimization of the catalyst for the Rh-catalyzed hydrosilylation of ketones showed that ligand 3 afforded the highest enantioselectivities for a wide variety of aryl alkyl and dialkyl ketones (up to 99% ee). A model for asymmetric induction in the hydrogenation reaction is discussed in the context of existing models, based on the absolute stereochemistry of the products and the X-ray crystal structures of catalyst precursors and intermediates.

  7. Regiocontrol by remote substituents. An enantioselective total synthesis of frenolicin B via a highly regioselective Diels-Alder reaction

    SciTech Connect

    Kraus, G.A.; Li, J. ); Gordon, M.S.; Jensen, J.H. )

    1993-06-30

    The quinone subunit is contained in a broad range of biologically important natural products such as frenolicin B, which is a member of the pyranonaphthoquinone family. The diverse biological activity of quinones has led to the development of several new synthetic methods for quinones. Among the pathways featuring a cycloaddition reaction, one of the most general methods for the regiospecific synthesis of substituted quinones was pioneered by H.J. Rapoport and others. This method involves the Diels-Alder reaction of a substituted quinone. As part of a program to evaluate the directing effects of functional groups not directly attached to the atoms undergoing Diels-Alder cycloaddition, we now report that remote substituents on a dienophile can confer excellent regioselectivity in Diels-Alder reactions. This work has led to an extremely direct synthesis of the pyranonaphthoquinone framework and to the first synthesis of frenolicin B (1). 19 refs., 1 fig.

  8. Enantioselective Total Synthesis of Mandelalide A and Isomandelalide A: Discovery of a Cytotoxic Ring-Expanded Isomer.

    PubMed

    Veerasamy, Nagarathanam; Ghosh, Ankan; Li, Jinming; Watanabe, Kazuhiro; Serrill, Jeffrey D; Ishmael, Jane E; McPhail, Kerry L; Carter, Rich G

    2016-01-27

    The total synthesis of mandelalide A and its ring-expanded macrolide isomer isomandelalide A has been achieved. Unexpected high levels of cytotoxicity were observed with the ring-expanded isomandelalide A with a rank order of potency: mandelalide A > isomandelalide A > mandelalide B. Key aspects of the synthesis include Ag-catalyzed cyclizations (AgCC's) to construct both the THF and THP rings present in the macrocycle, diastereoselective Sharpless dihydroylation of a cis-enyne, and lithium acetylide coupling with a chiral epoxide.

  9. Transition-metal-catalyzed enantioselective heteroatom-hydrogen bond insertion reactions.

    PubMed

    Zhu, Shou-Fei; Zhou, Qi-Lin

    2012-08-21

    Carbon-heteroatom bonds (C-X) are ubiquitous and are among the most reactive components of organic compounds. Therefore investigations of the construction of C-X bonds are fundamental and vibrant fields in organic chemistry. Transition-metal-catalyzed heteroatom-hydrogen bond (X-H) insertions via a metal carbene or carbenoid intermediate represent one of the most efficient approaches to form C-X bonds. Because of the availability of substrates, neutral and mild reaction conditions, and high reactivity of these transformations, researchers have widely applied transition-metal-catalyzed X-H insertions in organic synthesis. Researchers have developed a variety of rhodium-catalyzed asymmetric C-H insertion reactions with high to excellent enantioselectivities for a wide range of substrates. However, at the time that we launched our research, very few highly enantioselective X-H insertions had been documented primarily because of a lack of efficient chiral catalysts and indistinct insertion mechanisms. In this Account, we describe our recent studies of copper- and iron-catalyzed asymmetric X-H insertion reactions by using chiral spiro-bisoxazoline and diimine ligands. The copper complexes of chiral spiro-bisoxazoline ligands proved to be highly enantioselective catalysts for N-H insertions of α-diazoesters into anilines, O-H insertions of α-diazoesters into phenols and water, O-H insertions of α-diazophosphonates into alcohols, and S-H insertions of α-diazoesters into mercaptans. The iron complexes of chiral spiro-bisoxazoline ligands afforded the O-H insertion of α-diazoesters into alcohols and water with unprecedented enantioselectivities. The copper complexes of chiral spiro-diimine ligands exhibited excellent reactivity and enantioselectivity in the Si-H insertion of α-diazoacetates into a wide range of silanes. These transition-metal-catalyzed X-H insertions have many potential applications in organic synthesis because the insertion products, including chiral

  10. Catalysis-based enantioselective total synthesis of myxothiazole Z, (14S)-melithiazole G and (14S)-cystothiazole F.

    PubMed

    Colon, Aude; Hoffman, Thomas J; Gebauer, Julian; Dash, Jyotirmayee; Rigby, James H; Arseniyadis, Stellios; Cossy, Janine

    2012-11-04

    A common strategy for the stereoselective and protecting group-free total synthesis of the myxobacterial antibiotics myxothiazole Z, (14S)-melithiazole G and (14S)-cystothiazole F is described featuring an asymmetric organocatalytic transfer hydrogenation, a palladium-catalyzed Stille coupling and a cross-metathesis as the key steps.

  11. 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

  12. Enantioselective [4 + 1] Annulation Reactions of α-Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles.

    PubMed

    Zheng, Peng-Fei; Ouyang, Qin; Niu, Sheng-Li; Shuai, Li; Yuan, Yi; Jiang, Kun; Liu, Tian-Yu; Chen, Ying-Chun

    2015-07-29

    Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2'-methyl α-isocupreine (α-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing α-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, (1)H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated.

  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

    2015-02-02

    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.

  14. Access to Enantiopure 5-, 7-, and 5,7-Substituted cis-Decahydroquinolines: Enantioselective Synthesis of (-)-Cermizine B.

    PubMed

    Pinto, Alexandre; Griera, Rosa; Molins, Elies; Fernández, Israel; Bosch, Joan; Amat, Mercedes

    2017-04-07

    Stereoconvergent cyclocondensation reactions of (R)- or (S)-phenylglycinol with appropriately substituted cyclohexanone-based δ-keto esters are the key steps of short synthetic routes to enantiopure 5-, 7-, and 5,7-substituted cis-decahydroquinolines. The factors governing the stereoselectivity of the cyclocondensation are discussed. The potential of the methodology is illustrated by a protecting-group-free synthesis of the phlegmarine-type Lycopodium alkaloid (-)-cermizine B.

  15. Enantioselective Synthesis of Polycyclic Nitrogen Heterocycles by Rh-Catalyzed Alkene Hydroacylation: Constructing Six-Membered Rings in the Absence of Chelation Assistance

    PubMed Central

    2015-01-01

    Catalytic, enantioselective hydroacylations of N-allylindole-2-carboxaldehydes and N-allylpyrrole-2-carboxaldehydes are reported. In contrast to many alkene hydroacylations that form six-membered rings, these annulative processes occur in the absence of ancillary functionality to stabilize the acylrhodium(III) hydride intermediate. The intramolecular hydroacylation reactions generate 7,8-dihydropyrido[1,2-a]indol-9(6H)ones and 6,7-dihydroindolizin-8(5H)-ones in moderate to high yields with excellent enantioselectivities. PMID:25020184

  16. 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

    2015-03-06

    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.

  17. Enantioselective synthesis of 6-[fluorine-18]-fluro-l-dopa from no-carrier-added fluorine-18-fluoride

    SciTech Connect

    Lemaire, C.; Damhaut, P.; Plenvaux, A.

    1994-12-01

    A trimethylammonium veratraldehyde triflate was synthesized and used as a precursor for the asymmetric synthesis of 6-[{sup 18}F]fluoro-L-dopa. Its nucleophilic fluorination with {sup 18} F-fluoride produced by the {sup 18}O(p,n) {sup 18}F nuclear reaction on enriched {sup 18}O-water led to the corresponding no-carrier-added [{sup 18}F]fluoroveratraldehyde (45 {plus_minus} 5% EOB). Diiodosilane was used to prepare the corresponding [{sup 18}F] fluorobenzyl iodide (36.5 {plus_minus} 5.3% EOB). Alkylation of (S)-1-tert-boc-2-tert-butyl-3-methyl-4-imidazolidinone with this electrophilic agent, hydrolysis and purification by preparative high-pressure liquid chromatography made 6-[{sup 18}F]fluoro-L-dopa ready for human injection, in a 23% {plus_minus} 6% decay-corrected radiochemical yield. The enantiomeric purity and the specific activity were above 96% and 1 Cl/{mu}mole respectively. Through this procedure, starting from 250 mCi of {sup 18}F-fluoride, multimillicurie amounts (32 {plus_minus} 8.5 mCi) of no-carrier-added 6-[{sup 18}F]fluoro-L-dopa are now available at the end of synthesis (90 min) with a good radiochemical purity (more than 98%). 28 refs., 3 figs., 1 tab.

  18. 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

  19. The catalytic enantioselective synthesis of tetrahydroquinolines containing all-carbon quaternary stereocenters via the formation of aza-ortho-xylylene with 1,2-dihydroquinoline as a precursor.

    PubMed

    Li, Guangxun; Liu, Hongxin; Wang, Yingwei; Zhang, Shiqi; Lai, Shujun; Tang, Ling; Zhao, Jinzhong; Tang, Zhuo

    2016-02-07

    Tetrahydroquinolines () with an all-carbon quaternary stereocenter were effectively obtained via the in situ formation of aza-ortho-xylylene () with easily accessible 1,2-dihydroquinolines as precursors. The reaction was rationalized with chiral phosporic acid to afford chiral with high yield and excellent enantioselectivity.

  20. Synthesis of both enantiomers of hemiesters by enantioselective methanolysis of meso cyclic anhydrides catalyzed by alpha-amino acid-derived chiral thioureas.

    PubMed

    Manzano, Rubén; Andrés, José M; Muruzábal, María-Dolores; Pedrosa, Rafael

    2010-08-06

    Both ureas and thioureas derived from L- or D-valine act as bifunctional organocatalysts able to induce the enantioselective alcoholysis of mono-, bi-, and tricyclic meso anhydrides. The desymmetrization occurs in near quantitative yields and excellent enantiomeric ratios (up to >99:<1) under low catalyst loading. Both enantiomers of the hemiesters can be directly obtained by changing the configuration of the catalyst.

  1. Towards configurationally stable [4]helicenes: enantioselective synthesis of 12-substituted 7,8-dihydro[4]helicene quinones.

    PubMed

    Carreño, M Carmen; Enríquez, Alvaro; García-Cerrada, Susana; Sanz-Cuesta, M Jesús; Urbano, Antonio; Maseras, Feliu; Nonell-Canals, Alfons

    2008-01-01

    The synthesis of enantiopure C-12 methoxy- or alkyl-substituted 5,7,8,12b-tetrahydro[4]helicene quinones 16 and 17 and the 7,8-dihydroaromatic analogues 4 and 5 has been achieved from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone. In the first series, with a structure containing both central and helical chiralities, the R absolute configuration of the stereogenic carbon atom was defined after the asymmetric cycloaddition step, whereas the P or M helicity was shown to be dependent on the nature of the C-12 substituent. The size of this group was also defining the configurational stability of the final (P)-7,8-dihydro[4]helicene quinones 4 and 5. The interconversion barriers between the P and M helimers in the latter, computed with a DFT B3LYP method, matched well with the experimentally observed stability. Our study provided evidence that, in addition to steric effects, a small but significant role of electronic effects is governing the configurational stability of such helical quinones.

  2. Enantioselective Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2H)-ones and 2,3-Dihydropyridin-4(1H)-ones from β-Substituted β-Hydroxyaminoaldehydes

    PubMed Central

    2015-01-01

    The synthesis of 3,4-dihydro-1,2-oxazepin-5(2H)-ones and 2,3-dihydropyridin-4(1H)-ones from β-substituted β-hydroxyaminoaldehydes is reported. The β-hydroxyaminoaldehydes were prepared by enantioselective organocatalytic 1,4-addition of N-tert-butyl (tert-butyldimethylsilyl)oxycarbamate to α,β-unsaturated aldehydes (MacMillan protocol). Alkyne addition to the aldehydes followed by alcohol oxidation furnished N-Boc O-TBS-protected β-aminoynones. Removal of the TBS protecting group initiated a 7-endo-dig cyclization to yield previously unknown 3,4-dihydro-1,2-oxazepin-5(2H)-ones. Reductive cleavage of the N–O bond of the oxazepinones and Boc-deprotection provided 2-substituted 2,3-dihydropyridin-4(1H)-ones via 6-endo-trig cyclization. 2,3-Dihydropyridin-4(1H)-ones are versatile intermediates that have been used for the synthesis of many alkaloids. The new protocol allows the synthesis of 3-dihydropyridin-4(1H)-ones carrying an array of substituents at C2 that cannot be prepared from commercial β-amino acids or by one-carbon homologation of proteinogenic amino acids. The use of readily available β-hydroxylaminoaldehydes expands the utility of our previously reported method to prepare 2,3-dihydropyridin-4(1H)-ones from β-amino acids as the source of diversity and chirality. A broad substrate scope is possible because β-aminoaldehydes can be prepared from α,β-unsaturated aldehydes by an enantioselective organocatalytic process. PMID:24785413

  3. Bisguanidinium dinuclear oxodiperoxomolybdosulfate ion pair-catalyzed enantioselective sulfoxidation

    PubMed Central

    Zong, Lili; Wang, Chao; Moeljadi, Adhitya Mangala Putra; Ye, Xinyi; Ganguly, Rakesh; Li, Yongxin; Hirao, Hajime; Tan, Choon-Hong

    2016-01-01

    Catalytic use of peroxomolybdate for asymmetric transformations has attracted increasing attention due to its catalytic properties and application in catalysis. Herein, we report chiral bisguanidinium dinuclear oxodiperoxomolybdosulfate [BG]2+[(μ-SO4)Mo2O2(μ-O2)2(O2)2]2− ion pair, as a catalyst for enantioselective sulfoxidation using aqueous H2O2 as the terminal oxidant. The ion pair catalyst is isolatable, stable and useful for the oxidation of a range of dialkyl sulfides. The practical utility was illustrated using a gram-scale synthesis of armodafinil, a commercial drug, with the catalyst generated in situ from 0.25 mol% of bisguanidinium and 2.5 mol% of Na2MoO4·2H2O. Structural characterization of this ion pair catalyst has been successfully achieved using single-crystal X-ray crystallography. PMID:27869124

  4. Bisguanidinium dinuclear oxodiperoxomolybdosulfate ion pair-catalyzed enantioselective sulfoxidation

    NASA Astrophysics Data System (ADS)

    Zong, Lili; Wang, Chao; Moeljadi, Adhitya Mangala Putra; Ye, Xinyi; Ganguly, Rakesh; Li, Yongxin; Hirao, Hajime; Tan, Choon-Hong

    2016-11-01

    Catalytic use of peroxomolybdate for asymmetric transformations has attracted increasing attention due to its catalytic properties and application in catalysis. Herein, we report chiral bisguanidinium dinuclear oxodiperoxomolybdosulfate [BG]2+[(μ-SO4)Mo2O2(μ-O2)2(O2)2]2- ion pair, as a catalyst for enantioselective sulfoxidation using aqueous H2O2 as the terminal oxidant. The ion pair catalyst is isolatable, stable and useful for the oxidation of a range of dialkyl sulfides. The practical utility was illustrated using a gram-scale synthesis of armodafinil, a commercial drug, with the catalyst generated in situ from 0.25 mol% of bisguanidinium and 2.5 mol% of Na2MoO4.2H2O. Structural characterization of this ion pair catalyst has been successfully achieved using single-crystal X-ray crystallography.

  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. By-design enantioselective self-amplification based on non-covalent product-catalyst interactions

    NASA Astrophysics Data System (ADS)

    Storch, Golo; Trapp, Oliver

    2016-11-01

    The synthesis of enantiomerically pure compounds is of great importance in pharmaceuticals, fragrances and biological applications, and functions as a key to many processes in nature. Asymmetric catalysis using enantiomerically pure catalysts represents an efficient synthetic method to achieve this goal. The enantiomeric excess of the reaction product correlates with the enantiomeric purity of the catalysts, except for nonlinear behaviour, therefore the use of stereochemically flexible catalysts seems to complicate the control of stereoselectivity. Self-amplifying catalytic reactions are attractive, but a general rational design is highly challenging. Here we show that product interaction with chiral recognition sites attached to structurally flexible phoshoramidite-type catalysts can sense the chirality and induce enantioselectivity in the catalyst. Structural flexibility along with sensing of the chirality of the product molecules results in a rapid increase of enantioselectivity of the dynamic catalysts (Δe.e. of up to 76%) and a shift out of equilibrium. In contrast to stereodynamic catalysts controlled with cleavable chiral auxiliaries, the enantioselectivity does not decrease.

  7. By-design enantioselective self-amplification based on non-covalent product-catalyst interactions.

    PubMed

    Storch, Golo; Trapp, Oliver

    2017-02-01

    The synthesis of enantiomerically pure compounds is of great importance in pharmaceuticals, fragrances and biological applications, and functions as a key to many processes in nature. Asymmetric catalysis using enantiomerically pure catalysts represents an efficient synthetic method to achieve this goal. The enantiomeric excess of the reaction product correlates with the enantiomeric purity of the catalysts, except for nonlinear behaviour, therefore the use of stereochemically flexible catalysts seems to complicate the control of stereoselectivity. Self-amplifying catalytic reactions are attractive, but a general rational design is highly challenging. Here we show that product interaction with chiral recognition sites attached to structurally flexible phoshoramidite-type catalysts can sense the chirality and induce enantioselectivity in the catalyst. Structural flexibility along with sensing of the chirality of the product molecules results in a rapid increase of enantioselectivity of the dynamic catalysts (Δe.e. of up to 76%) and a shift out of equilibrium. In contrast to stereodynamic catalysts controlled with cleavable chiral auxiliaries, the enantioselectivity does not decrease.

  8. Asymmetric syntheses and transformations--tools for chirality multiplication in drug synthesis.

    PubMed

    Gawroński, Jacek

    2006-01-01

    A review of currently used methods for the synthesis and resolution of enantiomers of drugs and their precursors is presented. For the synthesis part the methods of diastereoselective as well as enantioselective synthesis are discussed, with particular consideration given to enantioselective catalysis with either metal complexes or biocatalysts. Desymmetrization processes are also included as methods to access enantiomerically pure compounds. Racemate resolution still remains an important method to obtain pure enantiomers and methods involving kinetic resolution in enzymatic or chemical systems, and particularly in connection with racemization (dynamic kinetic resolution) are on the rise in fine chemical industry, when applicable.

  9. Diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes catalyzed by a chiral Ni(OAc)(2) complex under mild conditions.

    PubMed

    Nakamura, Ayako; Lectard, Sylvain; Hashizume, Daisuke; Hamashima, Yoshitaka; Sodeoka, Mikiko

    2010-03-31

    A highly efficient, catalytic, diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes has been devised. The reaction was applicable to various substrates. Notably, the combination of endogenous and exogenous bases was effective, allowing a small amount of the catalyst (0.1-1 mol % Ni) to promote the reaction efficiently. The synthetic utility of this reaction was demonstrated in the synthesis of substituted pyrrolidine derivatives, whose stereochemistry is closely related to biologically important natural products such as kainic acid.

  10. Brønsted acid catalyzed phosphoramidic acid additions to alkenes: diastereo- and enantioselective halogenative cyclizations for the synthesis of C- and P-chiral phosphoramidates.

    PubMed

    Toda, Yasunori; Pink, Maren; Johnston, Jeffrey N

    2014-10-22

    The first highly diastereo- and enantioselective additions of a halogen and phosphoramidic acid to unactivated alkenes have been developed, catalyzed by a chiral Brønsted acid. A unique feature of these additions is the opportunity for stereocontrol at two noncontiguous chiral centers, carbon and phosphorus, leading to cyclic P-chiral phosphoramidates. In addition to their inherent value, the phosphoramidates are precursors to enantioenriched epoxy allylamines.

  11. Highly Enantioselective Direct Synthesis of Endocyclic Vicinal Diamines through Chiral Ru(diamine)-Catalyzed Hydrogenation of 2,2'-Bisquinoline Derivatives.

    PubMed

    Ma, Wenpeng; Zhang, Jianwei; Xu, Cong; Chen, Fei; He, Yan-Mei; Fan, Qing-Hua

    2016-10-04

    An asymmetric hydrogenation of 2,2'-bisquinoline and bisquinoxaline derivatives, catalyzed by chiral cationic ruthenium diamine complexes, was developed. A broad range of chiral endocyclic vicinal diamines were obtained in high yields with excellent diastereo- and enantioselectivity (up to 93:7 dl/meso and >99 % ee). These chiral diamines could be easily transformed into a new class of chiral N-heterocyclic carbenes (NHCs), which are important but difficult to access.

  12. Enantioselective Synthesis of Chiral Oxygen-Containing Heterocycles Using Copper-Catalyzed Aryl C-O Coupling Reactions via Asymmetric Desymmetrization.

    PubMed

    Zhang, Yong; Wang, Qiuyan; Wang, Ting; He, Huan; Yang, Wenqiang; Zhang, Xinhao; Cai, Qian

    2017-02-03

    An enantioselective desymmetric aryl C-O coupling reaction was demonstrated under the catalysis of CuI and a chiral cyclic diamine ligand. A series of chiral oxygen-containing heterocyclic units such as 2,3-dihydrobenzofurans, chromans, and 1,4-benzodioxanes with tertiary or quaternary stereocarbon centers were synthesized with this method. DFT calculations were also carried out for a better understanding of the model for enantiocontrol.

  13. 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.

  14. Enantioselective Michael addition of water.

    PubMed

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

    2015-02-09

    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.

  15. 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

  16. Palladium(II)-Catalyzed Enantioselective Reactions Using COP Catalysts.

    PubMed

    Cannon, Jeffrey S; Overman, Larry E

    2016-10-18

    Allylic amides, amines, and esters are key synthetic building blocks. Their enantioselective syntheses under mild conditions is a continuing pursuit of organic synthesis methods development. One opportunity for the synthesis of these building blocks is by functionalization of prochiral double bonds using palladium(II) catalysis. In these reactions, nucleopalladation mediated by a chiral palladium(II) catalyst generates a new heteroatom-substituted chiral center. However, reactions where nucleopalladation occurs with antarafacial stereoselectivity are difficult to render enantioselective because of the challenge of transferring chiral ligand information across the square-planar palladium complex to the incoming nucleophile. In this Account, we describe the development and use of enantiopure palladium(II) catalysts of the COP (chiral cobalt oxazoline palladacyclic) family for the synthesis of enantioenriched products from starting materials derived from prochiral allylic alcohols. We begin with initial studies aimed at rendering catalyzed [3,3]-sigmatropic rearrangements of allylic imidates enantioselective, which ultimately led to the identification of the significant utility of the COP family of Pd(II) catalysts. The first use of an enantioselective COP catalyst was reported by Richards' and our laboratories in 2003 for the enantioselective rearrangement of allylic N-arylimidates. Shortly thereafter, we discovered that the chloride-bridged COP dimer, [COP-Cl]2, was an excellent enantioselective catalyst for the rearrangement of (E)-allylic trichloroacetimidates to enantioenriched allylic trichloroacetamides, this conversion being the most widely used of the allylic imidate rearrangements. We then turn to discuss SN2' reactions catalyzed by the acetate-bridged COP dimer, [COP-OAc]2, which proceed by a unique mechanism to provide branched allylic esters and allylic phenyl ethers in high enantioselectivity. Furthermore, because of the unique nucleopalladation

  17. Rh-Catalyzed Chemo- and Enantioselective Hydrogenation of Allylic Hydrazones.

    PubMed

    Hu, Qiupeng; Hu, Yanhua; Liu, Yang; Zhang, Zhenfeng; Liu, Yangang; Zhang, Wanbin

    2017-01-23

    A highly efficient P-stereogenic diphosphine-rhodium complex was applied to the chemo- and enantioselective hydrogenation of allylic hydrazones for the synthesis of chiral allylic hydrazines in 89-96 % yields and with 82-99 % ee values. This methodology was successfully applied to the preparation of versatile chiral allylic amine derivatives.

  18. 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…

  19. Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release.

    PubMed

    Yin, Junfa; Cui, Yue; Yang, Gengliang; Wang, Hailin

    2010-11-07

    Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release are fabricated by the combination of template synthesis and ATRP grafting. The release of R-propranolol from the imprinted nanotubes in rats is restricted while the release of pharmacologically active S-enantiomer is greatly promoted.

  20. Enantioselective Hydroaminomethylation of Olefins Enabled by Rh/Brønsted Acid Relay Catalysis.

    PubMed

    Meng, Jing; Li, Xing-Han; Han, Zhi-Yong

    2017-03-03

    Herein, by employing a rhodium catalyst with a commercial ligand and a phosphoric acid catalyst, highly chemo-, regio-, and enantioselective hydroaminomethylation of olefins is realized through a relay catalytic hydroformylation/dynamic kinetic reductive amination process. The method features mild conditions (1 bar of syngas, room temperature in most cases), high yields (up to 99%), and high enantioselectivities (up to >99.5:0.5 er). Besides styrenes, acrylamides also provided the products with high yields and enantioselectivities. Aliphatic alkenes and vinyl esters are also applicable for the current method, albeit lower yields and enantioselectivities were obtained.

  1. Palladium(II)-catalyzed enantioselective C(sp³)-H activation using a chiral hydroxamic acid ligand.

    PubMed

    Xiao, Kai-Jiong; Lin, David W; Miura, Motofumi; Zhu, Ru-Yi; Gong, Wei; Wasa, Masayuki; Yu, Jin-Quan

    2014-06-04

    An enantioselective method for Pd(II)-catalyzed cross-coupling of methylene β-C(sp(3))-H bonds in cyclobutanecarboxylic acid derivatives with arylboron reagents is described. High yields and enantioselectivities were achieved through the development of chiral mono-N-protected α-amino-O-methylhydroxamic acid (MPAHA) ligands, which form a chiral complex with the Pd(II) center. This reaction provides an alternative approach to the enantioselective synthesis of cyclobutanecarboxylates containing α-chiral quaternary stereocenters. This new class of chiral catalysts also show promises for enantioselective β-C(sp(3))-H activation of acyclic amides.

  2. 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.).

  3. Enantioselective Synthesis of 5,7-Bicyclic Ring Systems from Axially Chiral Allenes Using a Rh(I)-Catalyzed Cyclocarbonylation Reaction

    PubMed Central

    Grillet, Francois; Brummond, Kay M.

    2013-01-01

    A transfer of chirality in an intramolecular Rh(I)-catalyzed allenic Pauson-Khand reaction (APKR) to access tetrahydroazulenones, tetrahydrocyclopenta[c]azepinones and dihydrocyclopenta[c]oxepinones enantioselectively (22 – 99% ee) is described. The substitution pattern of the allene affected the transfer of chiral information. Complete transfer of chirality was obtained for all trisubstituted allenes, but loss of chiral information was observed for disubstituted allenes. This work constitutes the first demonstration of a transfer of chiral information from an allene to the 5-position of a cyclopentenone using a cyclocarbonylation reaction. The absolute configuration of the corresponding cyclocarbonylation product was also established, something that is rarely done. PMID:23485149

  4. Metal-Catalyzed Asymmetric Michael Addition in Natural Product Synthesis.

    PubMed

    Hui, Chunngai; Pu, Fan; Xu, Jing

    2016-12-19

    Asymmetric catalysis for chiral compound synthesis is a rapidly growing field in modern organic chemistry. Asymmetric catalytic processes have been indispensable for the synthesis of enantioselective materials to meet demands from various fields. Michael addition has been used extensively for the construction of C-C bonds under mild conditions. With the discovery and development of organo- and metal-catalyzed asymmetric Michael additions, the synthesis of enantioselective and/or diastereoselective Michael adducts has become possible and increasingly prevalent in the literature. In particular, metal-catalyzed asymmetric Michael addition has been employed as a key reaction in natural product synthesis for the construction of contiguous quaternary stereogenic center(s), which is still a difficult task in organic synthesis. Previously reported applications of metal-catalyzed asymmetric Michael additions in natural product synthesis are presented here and discussed in depth.

  5. Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd-catalyzed cross-coupling.

    PubMed

    Xu, Shiqing; Oda, Akimichi; Kamada, Hirofumi; Negishi, Ei-ichi

    2014-06-10

    Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)-Cu- or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80-88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols.

  6. Catalytic enantioselective construction of tetrasubstituted carbons by self-assembled poly rare earth metal complexes.

    PubMed

    Shibasaki, Masakatsu; Kanai, Motomu

    2007-07-07

    Rare earth metal-based enantioselective catalysts that can promote practical cyanation reactions of ketones and ketoimines were developed. These catalytic enantioselective tetrasubstituted carbon-forming reactions are useful platforms for the synthesis of biologically active compounds. ESI-MS and crystallographic studies of the asymmetric catalysts revealed that the active catalysts are polymetallic complexes produced through the assembly of modules. The higher-order structure of the polymetallic complexes has strong effects on catalyst activity and enantioselectivity. Controlling the higher-order structure of artificial polymetallic asymmetric catalysts is a new strategy for optimizing asymmetric catalysts. Recent progress in this approach is also described.

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

    PubMed

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

    2016-09-15

    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.

  8. 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.

  9. Direct enantioselective conjugate addition of carboxylic acids with chiral lithium amides as traceless auxiliaries.

    PubMed

    Lu, Ping; Jackson, Jeffrey J; Eickhoff, John A; Zakarian, Armen

    2015-01-21

    Michael addition is a premier synthetic method for carbon-carbon and carbon-heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B.

  10. 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.

  11. 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

  12. Enantioselective Cycloaddition Reactions Catalyzed by BINOL-Derived Phosphoric Acids and N-Triflyl Phosphoramides: Recent Advances.

    PubMed

    Held, Felix E; Grau, Dominik; Tsogoeva, Svetlana B

    2015-09-03

    Over the last several years there has been a huge increase in the development and applications of new efficient organocatalysts for enantioselective pericyclic reactions, which represent one of the most powerful types of organic transformations. Among these processes are cycloaddition reactions (e.g., [3+2]; formal [3+3]; [4+2]; vinylogous [4+2] and 1,3-dipolar cycloadditions), which belong to the most utilized reactions in organic synthesis of complex nitrogen- and oxygen-containing heterocyclic molecules. This review presents the breakthrough realized in this field using chiral BINOL-derived phosphoric acids and N-triflyl phosphoramide organocatalysts.

  13. Synthesis, Characterization and Application of Functional Carbon Nano Materials

    DTIC Science & Technology

    2014-05-05

    NO. 0704-0188 3. DATES COVERED (From - To) - UU UU UU UU 22-07-2014 Approved for public release; distribution is unlimited. SYNTHESIS ...CHARACTERIZATION AND APPLICATION OFFUNCTIONAL CARBON NANO MATERIALS The synthesis , characterizations and applications of carbon nanomaterials, including carbon...PR 00931 -1790 ABSTRACT SYNTHESIS , CHARACTERIZATION AND APPLICATION OFFUNCTIONAL CARBON NANO MATERIALS Report Title The synthesis , characterizations

  14. Isothiourea-catalysed enantioselective pyrrolizine synthesis: synthetic and computational studies† †Electronic supplementary information (ESI) available: NMR spectra, HPLC analysis and computational co-ordinates. Data available.12 CCDC 1483759. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ob01557c Click here for additional data file. Click here for additional data file. Click here for additional data file.

    PubMed Central

    Stark, Daniel G.; Williamson, Patrick; Gayner, Emma R.; Musolino, Stefania F.; Kerr, Ryan W. F.; Taylor, James E.; Slawin, Alexandra M. Z.; O'Riordan, Timothy J. C.

    2016-01-01

    The catalytic enantioselective synthesis of a range of cis-pyrrolizine carboxylate derivatives with outstanding stereocontrol (14 examples, >95 : 5 dr, >98 : 2 er) through an isothiourea-catalyzed intramolecular Michael addition-lactonisation and ring-opening approach from the corresponding enone acid is reported. An optimised and straightforward three-step synthetic route to the enone acid starting materials from readily available pyrrole-2-carboxaldehydes is delineated, with benzotetramisole (5 mol%) proving the optimal catalyst for the enantioselective process. Ring-opening of the pyrrolizine dihydropyranone products with either MeOH or a range of amines leads to the desired products in excellent yield and enantioselectivity. Computation has been used to probe the factors leading to high stereocontrol, with the formation of the observed cis-steroisomer predicted to be kinetically and thermodynamically favoured. PMID:27489030

  15. 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

  16. Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones.

    PubMed

    Craig, Robert A; Loskot, Steven A; Mohr, Justin T; Behenna, Douglas C; Harned, Andrew M; Stoltz, Brian M

    2015-11-06

    The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee's up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

  17. Gold(I)-Catalyzed Enantioselective Ring Expansion of Allenylcyclopropanols

    PubMed Central

    Kleinbeck, Florian; Toste, F. Dean

    2009-01-01

    The asymmetric gold(I)-catalyzed ring expansion of 1-allenylcyclopropanols is described. The method provides synthetically valuable cyclobutanones with a vinyl-substituted quaternary stereogenic center in high enantioselectivities and yields. The method shows a broad substrate scope, tolerating protected alcohols and amines, alkenes, unsaturated esters and acetals. The reaction is easily adjustable to large scale synthesis, leading to product formation without significant loss of selectivity or yield with only 0.5 mol% catalyst loading. PMID:19530649

  18. 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...

  19. 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

  20. Palladium-Catalyzed Decarbonylative Dehydration for the Synthesis of α-Vinyl Carbonyl Compounds and Total Synthesis of (−)-Aspewentin A, B, and C

    PubMed Central

    Liu, Yiyang; Virgil, Scott C.; Grubbs, Robert H.; Stoltz, Brian M.

    2015-01-01

    The direct α-vinylation of carbonyl compounds that forms a quaternary stereocenter is a challenging transformation. We discovered that δ-oxocarboxylic acids can serve as masked vinyl compounds and be unveiled by palladium-catalyzed decarbonylative dehydration. The carboxylic acids are readily available through enantioselective acrylate addition or asymmetric allylic alkylation. A variety of α-vinyl quaternary carbonyl compounds are obtained in good yields, and an application in the first enantioselective total synthesis of (−)-aspewentin A, B, and C is demonstrated. PMID:26230413

  1. 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.

  2. 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...

  3. Development of (trimethylsilyl)ethyl ester protected enolates and applications in palladium-catalyzed enantioselective allylic alkylation: intermolecular cross-coupling of functionalized electrophiles.

    PubMed

    Reeves, Corey M; Behenna, Douglas C; Stoltz, Brian M

    2014-05-02

    The development of (trimethylsilyl)ethyl ester protected enolates is reported. The application of this class of compounds in palladium-catalyzed asymmetric allylic alkylation is explored, yielding a variety of α-quaternary six- and seven-membered ketones and lactams. Independent coupling partner synthesis engenders enhanced allyl substrate scope relative to traditional β-ketoester substrates; highly functionalized α-quaternary ketones generated by the union of (trimethylsilyl)ethyl β-ketoesters and sensitive allylic alkylation coupling partners serve to demonstrate the utility of this method for complex fragment coupling.

  4. 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.

  5. Enantioselective Synthesis of the C1-C6 and C7-C23 Fragments of the Proposed Structure of Iriomoteolide 1a

    PubMed Central

    Crimmins, Michael T.; Dechert, Anne-Marie R.

    2012-01-01

    Synthesis of the C1-C6 and C7-C23 fragments of the proposed structure of iriomoteolide 1a has been accomplished. Key steps include a cross metathesis to form the C15-C16 E olefin and a chelation controlled Grignard addition to form the tertiary alcohol at C14. Notably, 7 of the 9 stereocenters of the proposed structure have been set using various aldol reactions employing metallo enolates of thiazolidinethiones. PMID:22512249

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

    PubMed

    Jammer, Shifra; Gelman, Faina; Lev, Ovadia

    2016-03-29

    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.

  7. 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

  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. Tetrazolium compounds: synthesis and applications in medicine.

    PubMed

    Wei, Cheng-Xi; Bian, Ming; Gong, Guo-Hua

    2015-03-27

    Tetrazoles represent a class of five-membered heterocyclic compounds with polynitrogen electron-rich planar structural features. This special structure makes tetrazole derivatives useful drugs, explosives, and other functional materials with a wide range of applications in many fields of medicine, agriculture, material science, etc. Based on our research works on azoles and other references in recent years, this review covers reported work on the synthesis and biological activities of tetrazole derivatives.

  10. A Unified Strategy for Enantioselective Total Synthesis of Cladiellin and Briarellin Diterpenes: Total Synthesis of Briarellins E and F, and the Putative Structure of Alcyonin and Revision of Its Structure Assignment

    PubMed Central

    Corminboeuf, Olivier; Overman, Larry E.; Pennington, Lewis D.

    2009-01-01

    Enantioselective total syntheses of briarellin E (12) and briarellin F (13), as well as the structure originally proposed for the cladiellin diterpene alcyonin (10), have been realized. Comparison of the spectral data for synthetic 10, natural alcyonin, cladiellisin (33), and cladiellaperoxide (34), as well as chemical transformations of 10 and natural alcyonin, suggest that the structure of this coral metabolite is allylic peroxide 11. The unified approach detailed herein can be used to access both C4-deoxygenated and C4-oxygenated cladiellins and briarellins. The central step in these syntheses is acid-promoted condensation of (Z)-α,β-unsaturated aldehydes 17 with cyclohexadienyl diols 18, to form intermediates 16 incorporating the hexahydroisobenzofuran core and five stereocenters of these marine diterpenes (Scheme 1). PMID:19534538

  11. Colloidosomes: synthesis, properties and applications.

    PubMed

    Thompson, Kate L; Williams, Mark; Armes, Steven P

    2015-06-01

    Colloidosomes represent a rapidly expanding field with various applications in microencapsulation, including the triggered release of cargoes. With self-assembled shells comprising colloidal particles, they offer significant flexibility with respect to microcapsule functionality. This review explores the various types of particles and techniques that have been employed to prepare colloidosomes. The relative advantages and disadvantages of these routes are highlighted and their potential as microcapsules for both small molecule and macromolecular actives is evaluated.

  12. Graphene: Synthesis, bio-applications, and properties.

    PubMed

    Abbasi, Elham; Akbarzadeh, Abolfazl; Kouhi, Mohammad; Milani, Morteza

    2016-01-01

    The properties of graphene, carbon sheets that are only one atom wide, have led researchers and companies to consider its synthesis, properties, and the applications in numerous fields. High-quality graphene is physically powerful, light, nearly transparent, and an exceptional conductor of heat and electricity. Its interactions with other materials and with light and its naturally two-dimensional nature produce unique properties, such as the bipolar transistor effect, ballistic transport of charges, and large quantum oscillations. The following review introduces the many potential applications of graphene.

  13. Nanoceria as Antioxidant: Synthesis and Biomedical Applications.

    PubMed

    Karakoti, A S; Monteiro-Riviere, N A; Aggarwal, R; Davis, J P; Narayan, R J; Self, W T; McGinnis, J; Seal, S

    2008-03-01

    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 role of ceria nanoparticles (nanoceria) have been established, as well as the autocatalytic ability of nanoceria to regenerate under various environmental conditions. The synthesis of nanoceria in biocompatible media has also been reported along with cell viability in order to determine the potential use of nanoceria in biomedical applications.

  14. Enantiopure sulfoxides: recent applications in asymmetric synthesis.

    PubMed

    Carreño, M Carmen; Hernández-Torres, Gloria; Ribagorda, María; Urbano, Antonio

    2009-11-07

    Sulfoxides are nowadays recognised as powerful chiral auxiliaries that may participate in a wide range of asymmetric reactions. Their high configurational stability, the existence of several efficient methods allowing the access to both configurations as well as their synthetic versatility are characteristic features offering a tremendous potential to develop new applications. Significant recent advances leading to high asymmetric inductions in carbon-carbon and carbon-oxygen bond forming reactions, and applications of homochiral sulfoxides to atroposelective synthesis and asymmetric catalysis are discussed. New uses of sulfoxides in the design of chiroptical switches are also shown.

  15. Dendrimers: synthesis, applications, and properties

    NASA Astrophysics Data System (ADS)

    Abbasi, Elham; Aval, Sedigheh Fekri; Akbarzadeh, Abolfazl; Milani, Morteza; Nasrabadi, Hamid Tayefi; Joo, Sang Woo; Hanifehpour, Younes; Nejati-Koshki, Kazem; Pashaei-Asl, Roghiyeh

    2014-05-01

    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.

  16. Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines

    PubMed Central

    Rong, Jiawei; Collados, Juan F.; Ortiz, Pablo; Jumde, Ravindra P.; Otten, Edwin; Harutyunyan, Syuzanna R.

    2016-01-01

    α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N-sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure. PMID:28008909

  17. Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines

    NASA Astrophysics Data System (ADS)

    Rong, Jiawei; Collados, Juan F.; Ortiz, Pablo; Jumde, Ravindra P.; Otten, Edwin; Harutyunyan, Syuzanna R.

    2016-12-01

    α-Chiral amines are of significant importance in medicinal chemistry, asymmetric synthesis and material science, but methods for their efficient synthesis are scarce. In particular, the synthesis of α-chiral amines with the challenging tetrasubstituted carbon stereocentre is a long-standing problem and catalytic asymmetric additions of organometallic reagents to ketimines that would give direct access to these molecules are underdeveloped. Here we report a highly enantioselective catalytic synthesis of N-sulfonyl protected α-chiral silyl amines via the addition of inexpensive, easy to handle and readily available Grignard reagents to silyl ketimines. The key to this success was our ability to suppress any unselective background addition reactions and side reduction pathway, through the identification of an inexpensive, chiral Cu-complex as the catalytically active structure.

  18. Catalytic enantioselective [2,3]-rearrangements of amine N-oxides.

    PubMed

    Bao, Hongli; Qi, Xiangbing; Tambar, Uttam K

    2011-02-09

    The first Pd-catalyzed enantioselective [2,3]-rearrangement of allylic amine N-oxides is described, which formally represents an asymmetric Meisenheimer rearrangement. The mild reaction conditions enable the synthesis of chiral nonracemic aliphatic allylic alcohol derivatives with reactive functional groups. On the basis of preliminary studies, a cyclization-mediated mechanism is proposed.

  19. Metalloisoporphyrins: from synthesis to applications.

    PubMed

    Bhuyan, Jagannath

    2015-09-28

    An overview of the chemistry of isoporphyrin, the tautomer of porphyrin, whose existence was predicated by the Noble laureate Woodward, is presented with emphasis on hydroxy-isoporphyrins of tetra-aryl derivatives. The chemistry of metalloisoporphyrin has been discussed since the discovery of the first metallo-isoporphyrin by Dolphin and co-workers, as no comprehensive article is available on this beautiful macrocycle. Attention is paid to the possible applications of metalloisoporphyrins as photosensitizers in photodynamic therapy, as a near infra-red dye and as a reactive agent for different atom transfer reactions. Some important findings about reactivity and theoretical results of hydroxy-isoporphyrins are discussed. Furthermore, the approaches of heme oxidation via isoporphyrin as an intermediate to understand the heme oxygenase mechanism are discussed. The metalloisoporphyrins are discussed reviewing coordination modes, structural changes, electronic properties and biological relevance.

  20. A Concise and Highly Enantioselective Total Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines.

    PubMed

    Rastelli, Ettore J; Coltart, Don M

    2015-11-16

    A concise asymmetric (>99:1 e.r.) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless-derived diol is converted into either a trans or cis epoxide, and these are subsequently converted into (+)-anti- and (-)-syn-mefloquine, respectively. The synthetic (+)-anti- and (-)-syn-mefloquine samples were derivatized with (S)-(+)-mandelic acid tert-butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X-ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)-anti- as well as (-)-syn-mefloquine.

  1. Polyferrocenylsilanes: synthesis, properties, and applications.

    PubMed

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

    2016-10-07

    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.

  2. Enantioselective organo-cascade catalysis.

    PubMed

    Huang, Yong; Walji, Abbas M; Larsen, Catharine H; MacMillan, David W C

    2005-11-02

    A new strategy for organocatalysis based on the biochemical blueprints of biosynthesis has enabled a new laboratory approach to cascade catalysis. Imidazolidinone-based catalytic cycles, involving iminium and enamine activation, have been successfully combined to allow a large diversity of nucleophiles (furans, thiophenes, indoles, butenolides, hydride sources, tertiary amino lactone equivalents) and electrophiles (fluorinating and chlorinating reagents) to undergo sequential addition with a wide array of alpha,beta-unsaturated aldehydes. These new cascade catalysis protocols allow the invention of enantioselective transformations that were previously unknown, including the asymmetric catalytic addition of the elements of HF across a trisubstituted olefin. Importantly, these domino catalysis protocols can be mediated by a single imidazolidinone catalyst or using cycle-specific amine catalysts. In the latter case, cascade catalysis pathways can be readily modulated to provide a required diastereo- and enantioselective outcome via the judicious selection of the enantiomeric series of the amine catalysts. A central benefit of combining multiple asymmetric organocatalytic events into one sequence is the intrinsic requirement for enantioenrichment in the second induction cycle, as demonstrated by the enantioselectivities obtained throughout this study (>/=99% ee in all cases).

  3. Enantioselective Nitroaldol Reaction of α-Ketoesters Catalyzed by Cinchona Alkaloids

    PubMed Central

    Li, Hongming; Wang, Baomin; Deng, Li

    2011-01-01

    The development of highly enantioselective and general catalytic nitroaldol (Henry) reactions with ketones is a challenging yet desirable task in organic synthesis. In this communication, we report an asymmetric nitroaldol reaction with α-ketoesters catalyzed by a new C6′-OH cinchona alkaloid catalyst. This is the first highly efficient organocatalytic asymmetric Henry reaction with ketones. This reaction is operationally simple and affords high enantioselectivity as well as good to excellent yield for a broad range of α-ketoesters. PMID:16417358

  4. 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.

  5. Effect of the Metal Ion on the Enantioselectivity and Linkage Isomerization of Thiosemicarbazone Helicates.

    PubMed

    Romero, María J; Suárez, Vanesa; Fernández-Fariña, Sandra; Maneiro, Marcelino; Martínez-Núñez, Emilio; Zaragoza, Guillermo; González-Noya, Ana M; Pedrido, Rosa

    2017-04-06

    The effect of the metal ion and ligand design on the enantioselectivity and linkage isomerization of neutral cobalt and zinc bisthiosemicarbazone metallohelicates has been investigated in this work. The electrochemical synthesis has afforded the enantioselective formation of chirally pure cobalt helicates, and the ΛΛ isomer of a single enantiomer has been crystallized as only product for the cobalt methyl-substituted thiosemicarbazone helicate. Interestingly linkage isomers have been formed from zinc ethyl-substituted thiosemicarbazone helicate enantiomers for the first time. The co-existence of these isomers has been evaluated from the point of view of both experimental results and computational calculations.

  6. 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

  7. Enantioselective recognition at mesoporous chiral metal surfaces

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

    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.

  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. Organocatalytic enantioselective cascade Michael-alkylation reactions: synthesis of chiral cyclopropanes and investigation of unexpected organocatalyzed stereoselective ring opening of cyclopropanes.

    PubMed

    Xie, Hexin; Zu, Liansuo; Li, Hao; Wang, Jian; Wang, Wei

    2007-09-05

    The development of efficient methods for the facile construction of important molecular architectures is a central goal in organic synthesis. An unprecedented organocatalytic asymmetric cascade Michael-alkylation reaction of alpha,beta-unsaturated aldehydes with bromomalonates has been developed. The process, efficiently catalyzed by chiral diphenylprolinol TMS ether in the presence of base 2,6-lutidine, serves as a powerful approach to the preparation of synthetically and biologically important cyclopropanes in high levels of enantio- and diastereoselectivities. Remarkably, the power of the cascade process is fueled by its high efficiency of the production of two new C-C bonds, two new stereogenic centers, and one quaternary carbon center in one single operation, which otherwise is difficult to achieve by traditional strategies. Moreover, the beauty of the cascade process is further underscored by the nature of the product formation depending on the reaction conditions. With the alternation of base from 2,6-lutidine (1.1 equiv), which is effective for the cyclopropanations, to NaOAc (4.0 equiv), the spontaneous ring-opening of cyclopropanes takes place to lead to stereoselective (E) alpha-substituted malonate alpha,beta-unsaturated aldehydes. A possible reaction mechanism, which involves a Michael-alkylation-retro-Michael pathway, is proposed and verified by experimental studies. This investigation represents the first example of an organocatalyst-promoted ring opening of the cyclopropanes, whereas such reactions have been intensively explored by Lewis acid-based catalysis.

  10. Enantioselective copper-catalyzed carboetherification of unactivated alkenes.

    PubMed

    Bovino, Michael T; Liwosz, Timothy W; Kendel, Nicole E; Miller, Yan; Tyminska, Nina; Zurek, Eva; Chemler, Sherry R

    2014-06-16

    Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols which terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition-state calculations support a cis-oxycupration stereochemistry-determining step.

  11. Highly enantioselective proton-initiated polycyclization of polyenes.

    PubMed

    Surendra, Karavadhi; Corey, E J

    2012-07-25

    This report describes the synthesis of a range of chiral polycyclic molecules (tricyclic to pentacyclic) from achiral polyene precursors by enantioselective proton-initiated polycyclization promoted by the 1:1 complex of o,o'-dichloro-BINOL and SbCl(5). Excellent yields (ca. 90% per ring formed) and enantioselectivety (20:1 to 50:1) were obtained. The process is practical as well as efficient, because the chiral ligand is both readily prepared from R,R- or S,S-BINOL and easily recovered from the reaction mixture by extraction.

  12. 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

  13. Enantioselective Conjugate Allylation of Cyclic Enones

    PubMed Central

    Taber, Douglass F.; Gerstenhaber, David A.; Berry, James F.

    2011-01-01

    Enantioselective organocatalytic 1,2-allylation of a cyclic enone followed by anionic oxy-Cope rearrangement delivered the ketone as a mixture of diastereomers. This appears to be a general method for the net enantioselective conjugate allylation of cyclic enones. PMID:21830779

  14. Enantioselective Total Syntheses of (−)-Palau’amine, (−)- Axinellamines, and (−)-Massadines

    PubMed Central

    Seiple, Ian B.; Su, Shun; Young, Ian S.; Nakamura, Akifumi; Yamaguchi, Junichiro; Jørgensen, Lars; Rodriguez, Rodrigo A.; O’Malley, Daniel P.; Gaich, Tanja; Köck, Matthias; Baran, Phil S.

    2011-01-01

    Dimeric pyrrole-imidazole alkaloids represent a rich and topologically unique class of marine natural products. This full account will follow the progression of efforts that culminated in the enantioselective total syntheses of the most structurally ornate members of this family: the axinellamines, the massadines, and palau’amine. A bio-inspired approach capitalizing on the pseudo-symmetry of the members of this class is recounted, delivering a deschloro derivative of the natural product core. Next, the enantioselective synthesis of the chlorocyclopentane core featuring a scalable, catalytic, enantioselective Diels–Alder reaction of a 1-siloxydiene is outlined in detail. Finally, the successful divergent conversion of this core to each of the aforementioned natural products, and the ensuing methodological developments are described. PMID:21861522

  15. Enantioselective Pd-catalyzed allylation of acyclic α-fluorinated ketones.

    PubMed

    Wang, Wengui; Shen, Haiming; Wan, Xiao-Long; Chen, Qing-Yun; Guo, Yong

    2014-07-03

    Significant synthetic challenges remain for the asymmetric synthesis of tertiary α-fluoro ketones, which are potentially useful molecules for the development of drugs, agrochemicals, and functional materials. Herein, we describe the development of a method for the catalytic enantioselective synthesis of tertiary α-fluoro ketones via the Tsuji-Trost reaction of racemic acyclic α-fluorinated ketones. Enantioenriched acyclic α-cabonyl tertiary fluorides can be produced with the aid of a palladium/phosphinooxazoline catalyst.

  16. Enantioselective Intramolecular C–H Insertion Reactions of Donor–Donor Metal Carbenoids

    PubMed Central

    2015-01-01

    The first asymmetric insertion reactions of donor–donor carbenoids, i.e., those with no pendant electron-withdrawing groups, are reported. This process enables the synthesis of densely substituted benzodihydrofurans with high levels of enantio- and diastereoselectivity. Preliminary results show similar efficiency in the preparation of indanes. This new method is used in the first enantioselective synthesis of an oligoresveratrol natural product (E-δ-viniferin). PMID:25308822

  17. Enantioselective amine α-functionalization via palladium-catalysed C-H arylation of thioamides

    NASA Astrophysics Data System (ADS)

    Jain, Pankaj; Verma, Pritha; Xia, Guoqin; Yu, Jin-Quan

    2016-10-01

    Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, the development of methods to functionalize the α-methylene C-H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (-)-sparteine followed by Pd(0) catalysed cross-coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalysed enantioselective α-C-H coupling of a wide range of amines, which include ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C-H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

  18. Enantioselective amine α-functionalization via palladium catalyzed C–H arylation of thioamides

    PubMed Central

    Jain, Pankaj; Verma, Pritha; Xia, Guoqin; Yu, Jin-Quan

    2016-01-01

    Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, development of methods to functionalize the α-methylene C–H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (–)-sparteine followed by Pd(0) catalyzed cross coupling to prepare α-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalyzed enantioselective α-C–H coupling of a wide range of amines, including ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines, and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C–H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments. PMID:28282045

  19. Synthesis of complex fluorides for optical applications

    NASA Astrophysics Data System (ADS)

    Stepleton, Seth Eugene

    Large single crystals of alkali metal fluorides are desirable for many reasons. Fluoride laser crystals have a wide transmission range and on account of their low phonon energies, many efficient laser emissions have been obtained from 285 nm to 4.34 microm.1,2 Inorganic fluoride single crystals feature large bandgaps, very wide optical transmittance ranges from vacuum-ultraviolet (VUV) to mid-IR wavelength regions, lower refractive indices than those of oxides, and typically lower phonon energies (which drastically reduce multiphonon relaxation rates of rare earth ions).3 The main goal of this work was to investigate the hydrothermal synthesis of alkali metal fluorides. Melt techniques have been used thoroughly to research a variety of fluoride systems and showed many phases that were inaccessible due to incongruent melting or phase stability. The existence of these phases was shown but never characterized or grown as a crystalline material. Solution growth in supercritical water was an ideal way to attempt the synthesis of novel compounds and phases. New synthetic routes to known phases and compounds also arose as a part of this work. Optically clear colorless crystals of K2BeF4 were synthesized up to 2 mm in size, and showed no phase transitions up to 1029 K, which suggests paraelectricitys at room temperature, contradicting previous reports.4 Attempts to incorporate a rare earth ion into the fluoroberyllate lattice proved unsuccessful however reactions between beryllium fluoride and lanthanide fluorides could be exploited as a synthetic route to single crystal rare earth fluorides. Hydrothermal reactions with KF produced crystals of three different phases: hexagonal KY2F7, trigonal KYF4 and orthorhombic K2YF5. All were optically clear, colorless crystals, with the K2YF5 crystals growing the largest. This compound is beneficial due to its application as a radiation dosimeter and laser host. 5,6 Optical quality colorless crystals of RbY2F7 and CsY2F7 up to 4 mm in

  20. 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.

  1. 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.

  2. Chiral Bidentate NHC Ligands Based on the 1,1'-Binaphthyl Scaffold: Synthesis and Application in Transition-Metal-Catalyzed Asymmetric Reactions.

    PubMed

    Xu, Qin; Gu, Peng; Jiang, Hanchun; Wei, Yin; Shi, Min

    2016-12-01

    The use of the chiral 1,1'-binaphthyl scaffold to construct chiral ligands can be traced back for a long time. However, the development of bidentate NHC ligands based on the same backbone has only appeared recently. In this account, we describe the design and synthesis of a new family of chiral NHC ligands based on the 1,1'-binaphthyl scaffold and demonstrate the applications of these chiral NHC-metal complexes in the catalyzed oxidative kinetic resolution of secondary alcohols, asymmetric carbon-carbon bond formations, hydrosilylations, and cyclizations of 1,6-enynes. The chiral NHC ligands containing the 1,1'-binaphthyl backbone can be synthesized in good yields from enantiomerically pure 1,1'-binaphthyl-2,2'-diamine. These transition metals coordinated with chiral bidentate NHC ligands exhibit high catalytic activities and good enantioselectivities for a wide range of metal-catalyzed asymmetric reactions.

  3. Recent applications of polymer supported organometallic catalysts in organic synthesis.

    PubMed

    Kann, Nina

    2010-09-07

    Recent developments concerning the application of polymer supported organometallic reagents in solid phase synthesis are reviewed, with a special focus on methodology for carbon-carbon formation. Examples of reactions that are covered include the classical Suzuki, Sonogashira and Heck coupings, but also aryl amination, epoxide opening, rearrangements, metathesis and cyclopropanation. Applications in the field of asymmetric synthesis are also discussed.

  4. Enantioselective determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study.

    PubMed

    Sun, Luning; Cao, Yang; Jiao, Huiwen; Fang, Yunqian; Yang, Zhicheng; Bian, Mingliang; Zhang, Hongwen; Gong, Xiaojian; Wang, Yongqing

    2015-11-01

    A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with tandem mass spectrometry. Lansoprazole enantiomers and internal standard (esomeprazole) were extracted from plasma using acetonitrile as protein precipitating agent. Baseline chiral separation was achieved within 9.0 min on a Chiralpak IC column (150 mm × 4.6 mm, 5 μm) with the column temperature of 30°C. The mobile phase consisted of 10 mM ammonium acetate solution containing 0.05% acetic acid/acetonitrile (50:50, v/v). The mass spectrometric analysis was performed using a QTrap 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. The multiple reactions monitoring transitions of m/z 370.1→252.1 and 346.1→198.1 were used to quantify lansoprazole enantiomers and esomeprazole, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-3000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was -3.8 to 3.3%. Analytes were stable during the study. No chiral inversion was observed during sample storage, preparation procedure and analysis. The method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of dexlansoprazole or racemic lansoprazole.

  5. 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.

  6. A Tethered Ru-S Complex with an Axial Chiral Thiolate Ligand for Cooperative Si-H Bond Activation: Application to Enantioselective Imine Reduction.

    PubMed

    Wübbolt, Simon; Maji, Modhu Sudan; Irran, Elisabeth; Oestreich, Martin

    2017-02-13

    An axial chiral version of the 2,6-dimesitylphenyl group attached to sulfur is reported. Its multistep preparation starts from (S)-binol, and the thiol group is established by a racemization-free thermal Newman-Kwart rearrangement. The new chiral thiolate ligand decorated with one mesityl group is used in the synthesis of a tethered ruthenium chloride complex. Its spectroscopic characterization revealed solvent-dependent epimerization at the ruthenium center. The major diastereomer is crystallographically characterized. Chloride abstraction with tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF4) yields the corresponding coordinatively unsaturated ruthenium complex with the Ru-S bond exposed. Si-H bond activation at this Ru-S bond proceeds in syn fashion but with moderate facial selectivity (d.r. = 70:30), generating diastereomeric chiral-at-ruthenium hydrosilane adducts. Their application to catalytic imine hydrosilylation led to promising enantioinduction (40% ee), thereby providing proof of concept for asymmetric catalysis involving cooperative Si-H bond activation.

  7. Monofunctional gold nanoparticles: synthesis and applications

    NASA Astrophysics Data System (ADS)

    Huo, Qun; Worden, James G.

    2007-12-01

    The ability to control the assembly of nanoparticle building blocks is critically important for the development of new materials and devices. The properties and functions of nanomaterials are not only dependent on the size and properties of individual particles, but also the interparticle distance and interactions. In order to control the structures of nanoassemblies, it is important to first achieve a precise control on the chemical functionality of nanoparticle building blocks. This review discusses three methods that have been reported recently for the preparation of monofunctional gold nanoparticles, i.e., nanoparticles with a single chemical functional group attached to each particle. The advantages and disadvantages of the three methods are discussed and compared. With a single functional group attached to the surface, one can treat such nanoparticles as molecular building blocks to react with other molecules or nanoparticles. In other words, by using appropriate chemical reactions, nanoparticles can be linked together into nanoassemblies and materials by covalent bonds, similar to the total chemical synthesis of complicated organic compounds from smaller molecular units. An example of using this approach for the synthesis of nanoparticle/polymer hybrid materials with optical limiting properties is presented. Other potential applications and advantages of covalent bond-based nanoarchitectures vs. non-covalent interaction-based supramolecular self-assemblies are also discussed briefly in this review.

  8. Cu-catalyzed enantioselective allylic alkylation with organolithium reagents.

    PubMed

    Hornillos, Valentín; Guduguntla, Sureshbabu; Fañanás-Mastral, Martín; Pérez, Manuel; Bos, Pieter H; Rudolph, Alena; Harutyunyan, Syuzanna R; Feringa, Ben L

    2017-03-01

    This protocol describes a method for the catalytic enantioselective synthesis of tertiary and quaternary carbon stereogenic centers, which are widely present in pharmaceutical and natural products. The method is based on the direct reaction between organolithium compounds, which are cheap, readily available and broadly used in chemical synthesis, and allylic electrophiles, using chiral copper catalysts. The methodology involves the asymmetric allylic alkylation (AAA) of allyl bromides, chlorides and ethers with organolithium compounds using catalyst systems based on Cu-Taniaphos and Cu-phosphoramidites. The protocol contains a complete description of the reaction setup, a method based on (1)H-NMR, gas chromatography-mass spectrometry (GC-MS) and chiral HPLC for assaying the regioselectivity and enantioselectivity of the product, and isolation, purification and characterization procedures. Six Cu-catalyzed AAA reactions between different organolithium reagents and allylic systems are detailed in the text as representative examples of these procedures. These reactions proceed within 1-10 h, depending on the nature of the allylic substrate (bromide, chloride, or ether and disubstituted or trisubstituted) or the chiral ligand used (Taniaphos or phosphoramidite). However, the entire protocol, including workup and purification, generally requires an additional 4-7 h to complete.

  9. Tetracalcium phosphate: Synthesis, properties and biomedical applications.

    PubMed

    Moseke, C; Gbureck, U

    2010-10-01

    Monoclinic tetracalcium phosphate (TTCP, Ca(4)(PO(4))(2)O), also known by the mineral name hilgenstockite, is formed in the (CaO-P(2)O(5)) system at temperatures>1300 degrees C. TTCP is the only calcium phosphate with a Ca/P ratio greater than hydroxyapatite (HA). It appears as a by-product in plasma-sprayed HA coatings and shows moderate reactivity and concurrent solubility when combined with acidic calcium phosphates such as dicalcium phosphate anhydrous (DCPA, monetite) or dicalcium phosphate dihydrate (DCPD, brushite). Therefore it is widely used in self-setting calcium phosphate bone cements, which form HA under physiological conditions. This paper aims to review the synthesis and properties of TTCP in biomaterials applications such as cements, sintered ceramics and coatings on implant metals.

  10. 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.

  11. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    Amines with remote stereocentres (stereocentres 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 carbon-carbon 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.

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

    PubMed

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

    2016-02-01

    Amines with remote stereocentres (stereocentres 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 carbon-carbon 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.

  14. 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

  15. Enantioselective synthesis of helicenequinones and -bisquinones.

    PubMed

    Urbano, Antonio; Carreño, M Carmen

    2013-02-07

    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.

  16. Enantioselective Recognition by Chiral Supramolecular Gels.

    PubMed

    Zhang, Li; Jin, Qingxian; Liu, Minghua

    2016-10-06

    Chiral supramolecular gels, in which small organic molecules self-assemble into chiral nanostructures and entangle each other to immobilize solvents through various noncovalent interactions, can work as a matrix for enantioselective recognition on chiral analytes. Through gelation and the formation of well-defined nanostructures, the chiral sense of the component molecules can be accumulated or amplified, and thus, the enantioselective recognition ability can be enhanced. Furthermore, a chiral microenvironment formed in the gel networks could provide additional stereochemical recognition geometry and attribute to efficient recognition. In this focus review, enantioselective recognition on chiral analytes through chiral supramolecular gels, with either amplified signals or the gel-sol phase transition, is discussed. This review is expected to provide useful insights into the design and fabrication of supramolecular gel systems with chiral features and high enantioselectivity.

  17. ENANTIOSELECTIVITY IN THE BIODEGRADATION OF PCB ATROPISOMERS

    EPA Science Inventory

    Microcosms inoculated with sediment from two locations in a contaminated reservoir, Lake Hartwell, SC, USA, degraded certain PCB atropisomers enantioselectively while other atropisomers were degraded in racemic proportions. The microcosms were spiked with either 234-236 PCB (PCB...

  18. Synthesis, characterization and application of electrode materials

    SciTech Connect

    He, Lin

    1995-07-07

    It has been known that significant advances in electrochemistry really depend on improvements in the sensitivity, selectivity, convenience, and/or economy of working electrodes, especially through the development of new working electrode materials. The advancement of solid state chemistry and materials science makes it possible to provide the materials which may be required as satisfactory electrode materials. The combination of solid state techniques with electrochemistry expands the applications of solid state materials and leads to the improvement of electrocatalysis. The study of Ru-Ti4O7 and Pt-Ti4O7 microelectrode arrays as introduced in paper 1 and paper 4, respectively, focuses on their synthesis and characterization. The synthesis is described by high temperature techniques for Ru or Pt microelectrode arrays within a conductive Ti4O7ceramic matrix. The characterization is based on the data obtained by x-ray diffractometry, scanning electron microscopy, voltammetry and amperometry. These microelectrode arrays show significant enhancement in current densities in comparison to solid Ru and Pt electrodes. Electrocatalysis at pyrochlore oxide Bi2Ru2O7.3 and Bi2Ir2O7 electrodes are described in paper 2 and paper 3, respectively. Details are reported for the synthesis and characterization of composite Bi2Ru2O7.3 electrodes. Voltammetric data are examined for evidence that oxidation can occur with transfer of oxygen to the oxidation products in the potential region corresponding to anodic discharge of H2O with simultaneous evolution of O2. Paper 3 includes electrocatalytic activities of composite Bi2Ir2O7 disk electrodes for the oxidation of I- and the reduction of IO3-.

  19. 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.

  20. Diastereo- and enantioselective synthesis of (E)-2-Methyl-1,2-syn- and (E)-2-Methyl-1,2-anti-3-pentenediols via allenylboronate kinetic resolution with ((d)Ipc)2BH and aldehyde allylboration.

    PubMed

    Han, Jeng-Liang; Chen, Ming; Roush, William R

    2012-06-15

    Enantioselective hydroboration of racemic allenylboronate (±)-1 with 0.48 equiv of ((d)Ipc)(2)BH at -25 °C proceeds with efficient kinetic resolution and provides allylborane (R)-Z-4. When heated to 95 °C, allylborane (R)-Z-4 isomerizes to the thermodynamically more stable allylborane isomer (S)-E-7. Subsequent allylboration of aldehydes with (R)-Z-4 or (S)-E-7 at -78 °C followed by oxidative workup provides 1,2-syn- or 1,2-anti-diols, 2 or 3, respectively, in 87-94% ee.

  1. Highly enantioselective and anti-diastereoselective catalytic intermolecular glyoxylate-ene reactions: effect of the geometrical isomers of alkenes.

    PubMed

    Zhang, Xiang; Wang, Min; Ding, Ran; Xu, Yun-He; Loh, Teck-Peng

    2015-06-05

    An efficient method for the synthesis of homoallylic alcohols with high enantioselectivities and anti-diastereoselectivities via an In(III)-catalyzed intermolecular glyoxylate-ene reaction has been developed. The geometrical isomers of alkenes were shown to have different reactivities. Only the isomers of the alkenes having a proton β-cis to the substituent reacted in this catalytic system.

  2. 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

  3. 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

  4. Simultaneous enantioselective separation of azelastine and three of its metabolites for the investigation of the enantiomeric metabolism in rats. I. Liquid chromatography-ionspray tandem mass spectrometry and electrokinetic capillary chromatography.

    PubMed

    Heinemann, Ute; Blaschke, Gottfried; Knebel, Norbert

    2003-08-15

    Enantioselective separation methods and the enantioselective determination of the anti-allergic drug azelastine and of three of its main phase I metabolites in a biological matrix underwent chromatographic and electrophoretic investigations. An enantioselective assay of a coupling of HPLC using a beta-cyclodextrin chiral stationary phase to ionspray tandem mass spectrometry is presented. Additionally, this assay is compared to another enantioselective assay using electrokinetic capillary chromatography with beta-cyclodextrin and carboxymethyl-beta-cyclodextrin in polyacrylamide-coated capillaries. For capillary electrophoresis (CE) the importance of polyacrylamide coating for the validation of this separation method is highlighted. Extracted rat plasma samples of enantioselective metabolism studies were measured by both validated assays. Differences in the pharmacokinetics and pharmacodynamics were evaluated for the main substance azelastine and its main metabolite demethylazelastine. So, a first hint about the enantioselectivity of biotransformation of azelastine in rats was seen after oral application of either enantiomer or the racemate to rats.

  5. Asymmetric total synthesis of Apocynaceae hydrocarbazole alkaloids (+)-deethylibophyllidine and (+)-limaspermidine.

    PubMed

    Du, Ji-Yuan; Zeng, Chao; Han, Xiao-Jie; Qu, Hu; Zhao, Xian-He; An, Xian-Tao; Fan, Chun-An

    2015-04-01

    An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization. A unified strategy based on this key tandem methodology has been divergently explored for the asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)-deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich the tandem reaction design concerning the asymmetric catalytic assembly of a chiral all-carbon quaternary stereocenter contained in the densely functionalized hydrocarbazole synthons but also manifest the potential for the application of the asymmetric catalysis based on the para-dienone chemistry in asymmetric synthesis of natural products.

  6. Synthesis and characterization of advanced materials for Navy applications

    NASA Technical Reports Server (NTRS)

    Covino, J.; Lee, I.

    1994-01-01

    The synthesis of ceramics and ceramic coatings through the sol-gel process has extensive application with the United States Navy and a broad range of potential commercial applications as well. This paper surveys seven specific applications for which the Navy is investigating these advanced materials. For each area, the synthetic process is described and the characteristics of the materials are discussed.

  7. L-Proline Derived Bifunctional Organocatalysts: Enantioselective Michael Addition of Dithiomalonates to trans-β-Nitroolefins.

    PubMed

    Jin, Hui; Kim, Seung Tae; Hwang, Geum-Sook; Ryu, Do Hyun

    2016-04-15

    A series of novel L-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-β-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R)-phenibut in high yield.

  8. Enantioselective intramolecular aldehyde α-alkylation with simple olefins: direct access to homo-ene products.

    PubMed

    Comito, Robert J; Finelli, Fernanda G; MacMillan, David W C

    2013-06-26

    A highly selective method for the synthesis of asymmetrically substituted carbocycles and heterocycles from unactivated aldehyde-olefin precursors has been achieved via enantioselective SOMO-catalysis. Addition of a catalytically generated enamine radical cation across a pendent olefin serves to establish a general asymmetric strategy toward the production of a wide range of formyl-substituted rings with alkene transposition. Conceptually, this novel mechanism allows direct access to "homo-ene"-type products.

  9. Biocatalytic route to chiral acyloins: P450-catalyzed regio- and enantioselective α-hydroxylation of ketones.

    PubMed

    Agudo, Rubén; Roiban, Gheorghe-Doru; Lonsdale, Richard; Ilie, Adriana; Reetz, Manfred T

    2015-01-16

    P450-BM3 and mutants of this monooxygenase generated by directed evolution are excellent catalysts for the oxidative α-hydroxylation of ketones with formation of chiral acyloins with high regioselectivity (up to 99%) and enantioselectivity (up to 99% ee). This constitutes a new route to a class of chiral compounds that are useful intermediates in the synthesis of many kinds of biologically active compounds.

  10. 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.

  11. 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

  12. 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.

  13. Silver nanoparticles: Synthesis methods, bio-applications and properties.

    PubMed

    Abbasi, Elham; Milani, Morteza; Fekri Aval, Sedigheh; Kouhi, Mohammad; Akbarzadeh, Abolfazl; Tayefi Nasrabadi, Hamid; Nikasa, Parisa; Joo, San Woo; Hanifehpour, Younes; Nejati-Koshki, Kazem; Samiei, Mohammad

    2016-01-01

    Silver nanoparticles size makes wide range of new applications in various fields of industry. Synthesis of noble metal nanoparticles for applications such as catalysis, electronics, optics, environmental and biotechnology is an area of constant interest. Two main methods for Silver nanoparticles are the physical and chemical methods. The problem with these methods is absorption of toxic substances onto them. Green synthesis approaches overcome this limitation. Silver nanoparticles size makes wide range of new applications in various fields of industry. This article summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations with respect to the biomedical applicability and regulatory requirements concerning silver nanoparticles.

  14. Catalytic asymmetric synthesis of enantioenriched heterocycles bearing a C-CF3 stereogenic center.

    PubMed

    Huang, Yi-Yong; Yang, Xing; Chen, Zhuo; Verpoort, Francis; Shibata, Norio

    2015-06-08

    Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles.

  15. 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

  16. 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.

  17. Applications of the Wittig-Still rearrangement in organic synthesis.

    PubMed

    Rycek, Lukas; Hudlicky, Tomas

    2017-02-16

    This review traces the discovery of the Wittig-Still rearrangement and its applications in organic synthesis. Its relationship to Wittig rearrangements is discussed along with detailed analysis of E/Z- and diastereoselectivity. Modifications of the products arising from the Wittig-Still rearrangement are reviewed in the context of increased complexity in intermediates potentially useful in target oriented synthesis. Early applications of the Wittig-Still rearrangement to modifications of steroids are reviewed as are applications to various terpene and alkaloid natural product targets and miscellaneous compounds. To the best of our knowledge, the literature is covered through December 2016.

  18. 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.

  19. Bio-inspired synthesis of metal nanomaterials and applications.

    PubMed

    Huang, Jiale; Lin, Liqin; Sun, Daohua; Chen, Huimei; Yang, Dapeng; Li, Qingbiao

    2015-10-07

    This critical review focuses on recent advances in the bio-inspired synthesis of metal nanomaterials (MNMs) using microorganisms, viruses, plants, proteins and DNA molecules as well as their applications in various fields. Prospects in the design of bio-inspired MNMs for novel applications are also discussed.

  20. Solution synthesis of metal oxides for electrochemical energy storage applications.

    PubMed

    Xia, Xinhui; Zhang, Yongqi; Chao, Dongliang; Guan, Cao; Zhang, Yijun; Li, Lu; Ge, Xiang; Bacho, Ignacio Mínguez; Tu, Jiangping; Fan, Hong Jin

    2014-05-21

    This article provides an overview of solution-based methods for the controllable synthesis of metal oxides and their applications for electrochemical energy storage. Typical solution synthesis strategies are summarized and the detailed chemical reactions are elaborated for several common nanostructured transition metal oxides and their composites. The merits and demerits of these synthesis methods and some important considerations are discussed in association with their electrochemical performance. We also propose the basic guideline for designing advanced nanostructure electrode materials, and the future research trend in the development of high power and energy density electrochemical energy storage devices.

  1. 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.

  2. 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

  3. 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.

  4. Enantioselective, iridium-catalyzed monoallylation of ammonia.

    PubMed

    Pouy, Mark J; Stanley, Levi M; Hartwig, John F

    2009-08-19

    Highly enantioselective, iridium-catalyzed monoallylations of ammonia are reported. These reactions occur with electron-neutral, -rich, and -poor cinnamyl carbonates, alkyl and trityloxy-substituted allylic carbonates, and dienyl carbonates in moderate to good yields and excellent enantioselectivities. This process is enabled by the use of an iridium catalyst that does not require a Lewis acid for activation and that is stable toward a large excess of ammonia. This selective formation of primary allylic amines allows for one-pot syntheses of heterodiallylamines and allylic amides that are not otherwise accessible via iridium-catalyzed allylic amination without the use of blocking groups and protective group manipulations.

  5. Enantioselective, Iridium-Catalyzed Monoallylation of Ammonia

    PubMed Central

    Pouy, Mark J.; Stanley, Levi M.; Hartwig, John F.

    2009-01-01

    Highly enantioselective, iridium-catalyzed monoallylations of ammonia are reported. These reactions occur with electron-neutral, -rich, and -poor cinnamyl carbonates, alkyl and trityloxy-substituted allylic carbonates, and dienyl carbonates in moderate to good yields and excellent enantioselectivities. This process is enabled by the use of an iridium catalyst that does not require a Lewis acid for activation and that is stable toward a large excess of ammonia. This selective formation of primary allylic amines allows for one-pot syntheses of heterodiallylamines and allylic amides that are not otherwise accessible via iridium-catalyzed allylic amination without the use of blocking groups and protective group manipulations. PMID:19722644

  6. Structural insights into the γ-lactamase activity and substrate enantioselectivity of an isochorismatase-like hydrolase from Microbacterium hydrocarbonoxydans

    PubMed Central

    Gao, Shuaihua; Zhou, Yu; Zhang, Weiwei; Wang, Wenhe; Yu, You; Mu, Yajuan; Wang, Hao; Gong, Xinqi; Zheng, Guojun; Feng, Yue

    2017-01-01

    (+)-γ-lactamase catalyzes the specific hydrolysis of (+)-γ-lactam out of the racemic γ-lactam (2-Azabicyclo[2.2.1]hept-5-en-3-one) to leave optically pure (−)-γ-lactam, which is the key building block of antiviral drugs such as carbovir and abacavir. However, no structural data has been reported on how the enzymes bind the γ-lactams and achieve their enantioselectivities. We previously identified an isochorismatase-like hydrolase (IHL, Mh33H4-5540) with (+)-γ-lactamase activity, which constitutes a novel family of γ-lactamase. Here, we first discovered that this enzyme actually hydrolyzed both (+)- and (−)-γ-lactam, but with apparently different specificities. We determined the crystal structures of the apo-form, (+)-γ-lactam bound, and (−)-γ-lactam bound forms of the enzyme. The structures showed that the binding sites of both (+) and (−)-γ-lactam resemble those of IHLs, but the “cover” loop conserved in IHLs is lacking in the enzyme, probably resulting in its incomplete enantioselectivity. Structural, biochemical, and molecular dynamics simulation studies demonstrated that the steric clash caused by the binding-site residues, especially the side-chain of Cys111 would reduce the binding affinity of (−)-γ-lactam and possibly the catalytic efficiency, which might explain the different catalytic specificities of the enantiomers of γ-lactam. Our results would facilitate the directed evolution and application of Mh33H4-5540 in antiviral drug synthesis. PMID:28295028

  7. Carbohydrate-Based Lactones: Synthesis and Applications

    NASA Astrophysics Data System (ADS)

    Xavier, Nuno M.; Rauter, Amélia P.; Queneau, Yves

    The synthesis and uses of different kinds of carbohydrate-based lactones are described. This group of compounds includes aldonolactones, other related monocyclic lactones and bicyclic systems. The latter can arise from uronic acids, carboxymethyl ethers or glycosides, or from C-branched sugars.

  8. 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.

  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. 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

  11. 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.

  12. 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

  13. 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.

  14. DNA Duplex Engineering for Enantioselective Fluorescent Sensor.

    PubMed

    Hu, Yuehua; Lin, Fan; Wu, Tao; Zhou, Yufeng; Li, Qiusha; Shao, Yong; Xu, Zhiai

    2017-02-21

    The rapid identification of biomacromolecule structure that has a specific association with chiral enantiomers especially from natural sources will be helpful in developing enantioselective sensor and in speeding up drug exploitation. Herein, owing to its existence also in living cells, apurinic/apyrimidinic site (AP site) was first engineered into ds-DNA duplex to explore its competence in enantiomer selectivity. An AP site-specific fluorophore was utilized as an enantioselective discrimination probe to develop a straightforward chiral sensor using natural tetrahydropalmatine (L- and D-THP) as enantiomer representatives. We found that only L-THP can efficiently replace the prebound fluorophore to cause a significant fluorescence increase due to its specific binding with the AP site (two orders magnitude higher in affinity than binding with D-THP). The AP site binding specificity of L-THP over D-THP was assessed via intrinsic fluorescence, isothermal titration calorimetry, and DNA stability. The enantioselective performance can be easily tuned by the sequences near the AP site and the number of AP sites. A single AP site provides a perfect binding pocket to differentiate the chiral atom-induced structure discrepancy. We expect that our work will inspire interest in engineering local structures into a ds-DNA duplex for developing novel enantioselective sensors.

  15. Thiourea-Catalyzed Enantioselective Cyanosilylation of Ketones

    PubMed Central

    Fuerst, Douglas E.; Jacobsen, Eric N.

    2011-01-01

    The new chiral amino thiourea catalyst 3d promotes the highly enantioselective cyanosilylation of a wide variety of ketones. The hindered tertiary amine substituent plays a crucial role both with regard to stereoinduction and reactivity, suggesting a cooperative mechanism involving electrophile activation by thiourea and nucleophile activation by the amine. PMID:15969569

  16. 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

  17. 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.

  18. Film grain synthesis and its application to re-graining

    NASA Astrophysics Data System (ADS)

    Schallauer, Peter; Mörzinger, Roland

    2006-01-01

    Digital film restoration and special effects compositing require more and more automatic procedures for movie regraining. Missing or inhomogeneous grain decreases perceived quality. For the purpose of grain synthesis an existing texture synthesis algorithm has been evaluated and optimized. We show that this algorithm can produce synthetic grain which is perceptually similar to a given grain template, which has high spatial and temporal variation and which can be applied to multi-spectral images. Furthermore a re-grain application framework is proposed, which synthesises based on an input grain template artificial grain and composites this together with the original image content. Due to its modular approach this framework supports manual as well as automatic re-graining applications. Two example applications are presented, one for re-graining an entire movie and one for fully automatic re-graining of image regions produced by restoration algorithms. Low computational cost of the proposed algorithms allows application in industrial grade software.

  19. Multifunctional Nanomaterials: Design, Synthesis and Application Properties.

    PubMed

    Martinelli, Marisa; Strumia, Miriam Cristina

    2017-02-07

    The immense scope of variation in dendritic molecules (hyper-branching, nano-sized, hydrophobicity/hydrophilicity, rigidity/flexibility balance, etc.) and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. Dendritic-based materials are therefore viable alternatives to conventional polymers. The overall aim of this work is to show the advantages of dendronization processes by presenting the synthesis and characterization of three different dendronized systems: (I) microbeads of functionalized chitosan; (II) nanostructuration of polypropylene surfaces; and (III) smart dendritic nanogels. The particular properties yielded by these systems could only be achieved thanks to the dendronization process.

  20. Total Synthesis of (-)-Conolutinine.

    PubMed

    Feng, Xiangyang; Jiang, Guangde; Xia, Zilei; Hu, Jiadong; Wan, Xiaolong; Gao, Jin-Ming; Lai, Yisheng; Xie, Weiqing

    2015-09-18

    The first enantioselective synthesis of (-)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)2 was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.

  1. Synergistic effects on enantioselectivity of zwitterionic chiral stationary phases for separations of chiral acids, bases, and amino acids by HPLC.

    PubMed

    Hoffmann, Christian V; Pell, Reinhard; Lämmerhofer, Michael; Lindner, Wolfgang

    2008-11-15

    In an attempt to overcome the limited applicability scope of earlier proposed Cinchona alkaloid-based chiral weak anion exchangers (WAX) and recently reported aminosulfonic acid-based chiral strong cation exchangers (SCX), which are conceptionally restricted to oppositely charged solutes, their individual chiral selector (SO) subunits have been fused in a combinatorial synthesis approach into single, now zwitterionic, chiral SO motifs. The corresponding zwitterionic ion-exchange-type chiral stationary phases (CSPs) in fact combined the applicability spectra of the parent chiral ion exchangers allowing for enantioseparations of chiral acids and amine-type solutes in liquid chromatography using polar organic mode with largely rivaling separation factors as compared to the parent WAX and SCX CSPs. Furthermore, the application spectrum could be remarkably expanded to various zwitterionic analytes such as alpha- and beta-amino acids and peptides. A set of structurally related yet different CSPs consisting of either a quinine or quinidine alkaloid moiety as anion-exchange subunit and various chiral or achiral amino acids as cation-exchange subunits enabled us to derive structure-enantioselectivity relationships, which clearly provided strong unequivocal evidence for synergistic effects of the two oppositely charged ion-exchange subunits being involved in molecular recognition of zwitterionic analytes by zwitterionic SOs driven by double ionic coordination.

  2. 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.

  3. 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.

  4. Asymmetric organocatalytic methods for the synthesis of tetrahydropyrans and their application in total synthesis.

    PubMed

    Vetica, Fabrizio; Chauhan, Pankaj; Dochain, Simon; Enders, Dieter

    2017-03-21

    Recent advancement in the area of asymmetric organocatalysis led to the development of new methodologies for the construction of valuable enantiopure molecules, including various heterocycles. As one of the latter class of compounds tetrahydropyrans (THPs) constitute a core structure of a wide array of bioactive natural products. A noticeable growth has been observed in the asymmetric synthesis of THPs using small organic molecules as catalysts. This Tutorial Review describes the organocatalytic methods available to furnish THPs as well as the application of these methodologies in the total synthesis of THP-based natural products.

  5. Infrared colloidal lead chalcogenide nanocrystals: synthesis, properties, and photovoltaic applications.

    PubMed

    Fu, Huiying; Tsang, Sai-Wing

    2012-04-07

    Simple solution phase, catalyst-free synthetic approaches that offer monodispersed, well passivated, and non-aggregated colloidal semiconductor nanocrystals have presented many research opportunities not only for fundamental science but also for technological applications. The ability to tune the electrical and optical properties of semiconductor nanocrystals by manipulating the size and shape of the crystals during the colloidal synthesis provides potential benefits to a variety of applications including photovoltaic devices, light-emitting diodes, field effect transistors, biological imaging/labeling, and more. Recent advances in the synthesis and characterization of colloidal lead chalcogenide nanocrystals and the achievements in colloidal PbS or PbSe nanocrystals solar cells have demonstrated the promising application of infrared-emitting colloidal lead chalcogenide nanocrystals in photovoltaic devices. Here, we review recent progress in the synthesis and optical properties of colloidal lead chalcogenide nanocrystals. We focus in particular upon the size- and shape-controlled synthesis of PbS, PbSe, and PbTe nanocrystals by using different precursors and various stabilizing surfactants for the growth of the colloidal nanocrystals. We also summarize recent advancements in the field of colloidal nanocrystals solar cells based on colloidal PbS and PbSe nanocrystals.

  6. Controllable synthesis and biomedical applications of silver nanomaterials.

    PubMed

    Huang, Zhihai; Jiang, Xiaoli; Guo, Dawei; Gu, Ning

    2011-11-01

    Silver nanomaterials have lots of peculiar and exciting physical and chemical properties that are different from massive silver, so the synthesis and applications of silver nanomaterials have attracted a great deal of attention in the last decade. Currently, all kinds of silver nanomaterials having different shapes and sizes have been synthesized by many ingenious methods, and silver nanomaterials have exhibited extensive application prospects in many fields especially in biomedical aspect. In this article, the controllable synthesis of silver nanomaterials including nanorods, nanowires, nanotubes, nanoprisms, nanoplates, nanodisks, nanospheres, and nanopolyhedrons, etc. are reviewed. Silver nanomaterials are most utilized in the form of nanoparticles, so the main biomedical applications of silver nanoparticles, such as antibacterial and antiviral applications, antitumor applications, biosensors and biological labels, optical imaging and imaging intensifier, are discussed. Although antibacterial applications are still the most important aspects of silver nanomaterials at present, antitumor, optical sensors and imaging applications of silver nanomaterials have also shown good potential perspectives. More biomedical applications of silver nanomaterials still need to be exploited for the future, and the biological safety of silver nanomaterials also should be paid enough attention before their practical applications.

  7. 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.

  8. 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

  9. Complex Hollow Nanostructures: Synthesis and Energy-Related Applications.

    PubMed

    Yu, Le; Hu, Han; Wu, Hao Bin; Lou, Xiong Wen David

    2017-04-01

    Hollow nanostructures offer promising potential for advanced energy storage and conversion applications. In the past decade, considerable research efforts have been devoted to the design and synthesis of hollow nanostructures with high complexity by manipulating their geometric morphology, chemical composition, and building block and interior architecture to boost their electrochemical performance, fulfilling the increasing global demand for renewable and sustainable energy sources. In this Review, we present a comprehensive overview of the synthesis and energy-related applications of complex hollow nanostructures. After a brief classification, the design and synthesis of complex hollow nanostructures are described in detail, which include hierarchical hollow spheres, hierarchical tubular structures, hollow polyhedra, and multi-shelled hollow structures, as well as their hybrids with nanocarbon materials. Thereafter, we discuss their niche applications as electrode materials for lithium-ion batteries and hybrid supercapacitors, sulfur hosts for lithium-sulfur batteries, and electrocatalysts for oxygen- and hydrogen-involving energy conversion reactions. The potential superiorities of complex hollow nanostructures for these applications are particularly highlighted. Finally, we conclude this Review with urgent challenges and further research directions of complex hollow nanostructures for energy-related applications.

  10. 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

  11. Organocatalytic enantioselective Michael addition of cyclic hemiacetals to nitroolefins: a facile access to chiral substituted 5- and 6-membered cyclic ethers.

    PubMed

    Zhu, Yadong; Qian, Pengfei; Yang, Jiyang; Chen, Shaohua; Hu, Yanwei; Wu, Ping; Wang, Wei; Zhang, Wei; Zhang, Shilei

    2015-04-28

    An efficient aminocatalytic enantioselective Michael addition of readily available cyclic hemiacetals to nitroolefins has been developed. The strategy serves as a powerful approach to synthetically valuable chiral 3-substituted tetrahydrofurans (THFs) and tetrahydropyrans (THPs). The synthetic utilities of the versatile Michael adducts also have been demonstrated in the synthesis of 2,3-disubstituted cyclic ethers, α-substituted lactones and venlafaxine analogues.

  12. Upconversion Nanomaterials: Synthesis, Mechanism, and Applications in Sensing

    PubMed Central

    Chen, Jiao; Zhao, Julia Xiaojun

    2012-01-01

    Upconversion is an optical process that involves the conversion of lower-energy photons into higher-energy photons. It has been extensively studied since mid-1960s and widely applied in optical devices. Over the past decade, high-quality rare earth-doped upconversion nanoparticles have been successfully synthesized with the rapid development of nanotechnology and are becoming more prominent in biological sciences. The synthesis methods are usually phase-based processes, such as thermal decomposition, hydrothermal reaction, and ionic liquids-based synthesis. The main difference between upconversion nanoparticles and other nanomaterials is that they can emit visible light under near infrared irradiation. The near infrared irradiation leads to low autofluorescence, less scattering and absorption, and deep penetration in biological samples. In this review, the synthesis of upconversion nanoparticles and the mechanisms of upconversion process will be discussed, followed by their applications in different areas, especially in the biological field for biosensing. PMID:22736958

  13. Upconversion nanomaterials: synthesis, mechanism, and applications in sensing.

    PubMed

    Chen, Jiao; Zhao, Julia Xiaojun

    2012-01-01

    Upconversion is an optical process that involves the conversion of lower-energy photons into higher-energy photons. It has been extensively studied since mid-1960s and widely applied in optical devices. Over the past decade, high-quality rare earth-doped upconversion nanoparticles have been successfully synthesized with the rapid development of nanotechnology and are becoming more prominent in biological sciences. The synthesis methods are usually phase-based processes, such as thermal decomposition, hydrothermal reaction, and ionic liquids-based synthesis. The main difference between upconversion nanoparticles and other nanomaterials is that they can emit visible light under near infrared irradiation. The near infrared irradiation leads to low autofluorescence, less scattering and absorption, and deep penetration in biological samples. In this review, the synthesis of upconversion nanoparticles and the mechanisms of upconversion process will be discussed, followed by their applications in different areas, especially in the biological field for biosensing.

  14. 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.

  15. 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.

  16. Practical enantioselective process for a chiral phosphodiesterase-4 inhibitor.

    PubMed

    Chen, Cheng-Yi

    2005-11-01

    L-869298 is a potent and selective phosphodiesterase-4 (PDE4) inhibitor, which is potentially useful in the treatment of asthma and chronic obstructive pulmonary disorder. A catalytic asymmetric synthesis that is suitable for the preparation of kilogram quantities of L-869298, and which does not require the use of chromatography, has been developed to support the on-going drug development program of L-869298 at Merck Research Laboratories. The catalytic asymmetric hydrogenation of an aromatic heteroaromatic ketone afforded the corresponding alcohol in almost perfect enantioselectivity. Activation of the alcohol via formation of the 4-toluenesulfonate, followed by an unprecedented displacement of the tosylate via the lithium enolate of ethyl-3-pyridyl acetate N-oxide, generated the chiral tetra-substituted ethane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Deprotection of the displacement adduct followed by decarboxylation, afforded L-869298 in excellent overall yield. The methodology developed could be readily extended to the synthesis of several other chiral PDE4 inhibitors.

  17. Synthesis of boron nitride nanotubes and their applications.

    PubMed

    Kalay, Saban; Yilmaz, Zehra; Sen, Ozlem; Emanet, Melis; Kazanc, Emine; Çulha, Mustafa

    2015-01-01

    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.

  18. 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

  19. 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.

  20. Enantioselective synthesis of syn/anti-1,3-amino alcohols via proline-catalyzed sequential alpha-aminoxylation/alpha-amination and Horner-Wadsworth-Emmons olefination of aldehydes.

    PubMed

    Jha, Vishwajeet; Kondekar, Nagendra B; Kumar, Pradeep

    2010-06-18

    A novel and general method for asymmetric synthesis of both syn/anti-1,3-amino alcohols is described. The method uses proline-catalyzed sequential alpha-aminoxylation/ alpha-amination and Horner-Wadsworth-Emmons (HWE) olefination of aldehydes as the key step. By using this method, a short synthesis of a bioactive molecule, (R)-1-((S)-1-methylpyrrolidin-2-yl)-5-phenylpentan-2-ol, is also accomplished.

  1. Ordered mesoporous metal oxides: synthesis and applications.

    PubMed

    Ren, Yu; Ma, Zhen; Bruce, Peter G

    2012-07-21

    Great progress has been made in the preparation and application of ordered mesoporous metal oxides during the past decade. However, the applications of these novel and interesting materials have not been reviewed comprehensively in the literature. In the current review we first describe different methods for the preparation of ordered mesoporous metal oxides; we then review their applications in energy conversion and storage, catalysis, sensing, adsorption and separation. The correlations between the textural properties of ordered mesoporous metal oxides and their specific performance are highlighted in different examples, including the rate of Li intercalation, sensing, and the magnetic properties. These results demonstrate that the mesoporosity has a direct impact on the properties and potential applications of such materials. Although the scope of the current review is limited to ordered mesoporous metal oxides, we believe that the information may be useful for those working in a number of fields.

  2. Bis(oxazoline) Lewis acid catalyzed aldol reactions of pyridine N-oxide aldehydes--synthesis of optically active 2-(1-hydroxyalkyl)pyridine derivatives: development, scope, and total synthesis of an indolizine alkaloid.

    PubMed

    Landa, Aitor; Minkkilä, Anna; Blay, Gonzalo; Jørgensen, Karl Anker

    2006-04-24

    A new, short, and simplified procedure for the synthesis of optically active pyridine derivatives from pro-chiral pyridine-N-oxides is presented. The catalytic and asymmetric Mukaiyama aldol reaction between ketene silyl acetals and 1-oxypyridine-2-carbaldehyde derivatives catalyzed by chiral copper(II)-bis(oxazoline) complexes gave optically active 2-(hydroxyalkyl)- and 2-(anti-1,2-dihydroxyalkyl)pyridine derivatives in good yields and diastereoselectivities, and in excellent enantioselectivities-up to 99 % enantiomeric excess. As a synthetic application of the developed method, a full account for the asymmetric total synthesis of a nonnatural indolizine alkaloid is provided.

  3. 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.

  4. Palladium-Catalyzed, Enantioselective Heine Reaction

    PubMed Central

    2016-01-01

    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)–diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis. PMID:27398262

  5. Palladium-Catalyzed, Enantioselective Heine Reaction.

    PubMed

    Punk, Molly; Merkley, Charlotte; Kennedy, Katlyn; Morgan, Jeremy B

    2016-07-01

    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)-diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis.

  6. Nickel-catalyzed enantioselective arylation of pyridine†

    PubMed Central

    Lutz, J. Patrick; Chau, Stephen T.

    2016-01-01

    We report an enantioselective Ni-catalyzed cross coupling of arylzinc reagents with pyridiniumions formed in situ from pyridine and a chloroformate. This reaction provides enantioenriched 2-aryl-1,2-dihydropyridine products that can be elaborated to numerous piperidine derivatives with little or no loss in ee. This method is notable for its use of pyridine, a feedstock chemical, to build a versatile, chiral heterocycle in a single synthetic step. PMID:28058106

  7. Chiral GAP catalysts of phosphonylated imidazolidinones and their applications in asymmetric Diels-Alder and Friedel-Crafts reactions.

    PubMed

    Qiao, Shuo; Mo, Junming; Wilcox, Cody B; Jiang, Bo; Li, Guigen

    2017-02-21

    The design and synthesis of recyclable imidazolidinone catalysts using GAP chemistry/technique was described. Their applications in asymmetric Diels-Alder and Friedel-Crafts reactions with α,β-unsaturated aldehydes resulted in excellent yields and higher enantioselectivities than previous processes. As recyclable small molecular catalysts, phosphonylated imidazolidinones can be recovered and reused for up to three runs without costing significant decrease in catalytic activity.

  8. Highly enantioselective Michael addition of cyclohexanone to nitroolefins catalyzed by pyrrolidine-based bifunctional benzoylthiourea in water.

    PubMed

    Wang, Zhen-Yu; Ban, Shu-Rong; Yang, Meng-Chen; Li, Qing-Shan

    2016-11-01

    Organocatalysis and aqueous reactions are identified as the focus of the greening of chemistry. Combining these two strategies effectively remains an interesting challenge in organic synthesis. Herein, we used pyrrolidine-based benzoylthiourea 1c to catalyze the asymmetric Michael addition of cyclohexanone to various nitroolefins in water to afford the corresponding compounds in moderate to good yields, and with excellent diastereoselectivities (up to >99:1 dr) and enantioselectivities (up to 99% ee).

  9. Enantioselective Aminomethylamination of Conjugated Dienes with Aminals Enabled by Chiral Palladium Complex-Catalyzed C-N Bond Activation.

    PubMed

    Liu, Yang; Xie, Yinjun; Wang, Hongli; Huang, Hanmin

    2016-04-06

    A novel highly enantioselective aminomethylamination of conjugated dienes with aminals catalyzed by a chiral palladium complex ligated with BINOL-derived chiral diphosphinite has been successfully developed. This reaction proceeds via a Pd-catalyzed cascade C-N bond activation, aminomethylation, and asymmetric allylic amination reaction under mild reaction conditions, providing a unique and efficient strategy for the synthesis of enantiomerically pure allylic 1,3-diamines.

  10. Enantioselective α-Alkylation of Aldehydes by Photoredox Organocatalysis: Rapid Access to Pharmacophore Fragments from β-Cyanoaldehydes.

    PubMed

    Welin, Eric R; Warkentin, Alexander A; Conrad, Jay C; MacMillan, David W C

    2015-08-10

    The combination of photoredox catalysis and enamine catalysis has enabled the development of an enantioselective α-cyanoalkylation of aldehydes. This synergistic catalysis protocol allows for the coupling of two highly versatile yet orthogonal functionalities, allowing rapid diversification of the oxonitrile products to a wide array of medicinally relevant derivatives and heterocycles. This methodology has also been applied to the total synthesis of the lignan natural product (-)-bursehernin.

  11. Application of the aza-Diels-Alder reaction in the synthesis of natural products.

    PubMed

    Cao, Min-Hui; Green, Nicholas J; Xu, Sheng-Zhen

    2017-03-22

    The Diels-Alder reaction that involves a nitrogen atom in the diene or dienophile is termed the aza-Diels-Alder reaction. As well as the powerful all-carbon Diels-Alder reaction, the aza-Diels-Alder reaction has also played an important role in the total synthesis of natural products. Herein, we review various natural products using an aza-Diels-Alder reaction as a key step to their total synthesis, and divide the syntheses into inter- and intra-molecular aza-Diels-Alder reactions and a retro-aza-Diels-Alder reaction. Inter- and intra-molecular aza-Diels-Alder reactions involve an imine as an electron deficient dienophile and an imine as an electron deficient azadiene. The significance of the aza-Diels-Alder reaction for the construction of a six-membered ring containing nitrogen is tremendous, but the development of asymmetric, in particular catalytic enantioselective intramolecular aza-Diels-Alder reaction in the total synthesis of natural products remains highly challenging, and will no doubt see enormous advances in the future.

  12. 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.

  13. Synthesis of plasmonic nanocomposites for diverse applications.

    PubMed

    Avasthi, D K; Mishra, Y K; Singhal, R; Kabiraj, D; Mohapatra, S; Mohanta, B; Gohil, Nivedita K; Singh, N

    2010-04-01

    We report the synthesis of gold and silver nanostructures embedded in different dielectric matrices by atom beam co-sputtering, a novel technique. We have synthesized gold-silicon core shell nanostructures and Au-ZnO nanocomposite with tunable surface plasmon resonance (SPR) by atom beam co-sputtering and subsequent annealing. The Au-ZnO nanocomposite shows significant enhancement in intensity of Raman modes of fullerene molecules and therefore can help in surface enhanced Raman spectroscopy investigation of organic molecules. The synthesized Ag-polymer nanocomposite thin films show excellent features of broad SPR absorption extending upto IR region and a narrow transmission of light in UV region approximately 320 nm which could be of technological interest in solar absorbers and UV light filters respectively. The Ag-silica nanocomposite thin films show their utility in glucose sensing. The gold-silica nanocomposite thin films exhibit their possible use in detection of human ovarian cancer cells in a preliminary study. The shift in SPR peak of Au nanoparticles (NPs) present at the surface of silica synthesized by thermal evaporation and annealing, after attachment of biological molecules like proteins has been studied.

  14. Recent Advances in the Preparation and Application of Allylboron Species in Organic Synthesis.

    PubMed

    Diner, Colin; Szabó, Kálmán J

    2017-01-11

    In this Perspective we will highlight the most important recent breakthroughs in selective allylboron chemistry (both the synthesis and application of these species). In addition we will provide an outlook toward the future of this promising subfield of organic synthesis.

  15. 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

  16. 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

  17. 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...

  18. Synthesis of Chromophores for Nonlinear Optics Applications

    DTIC Science & Technology

    2010-03-12

    Investigacion de Quimica Aplicada Blvd. Enrique reyna, No. 140 Saltillo, Coahuila, Mexico 25253 AFOSR FA9550-09-1-0017 12 March 2010...PERFORMING ORGANIZATION REPORT NUMBER CENTRO DE INVESTIGACION EN QUIMICA APLICADA BLVD ENRIQUE REYNA NO 140 SALTILLO 25253 MEXICO...APPLICATIONS Eduardo Arias, Ivana Moggio and Ronald F. Ziolo Centro de Investigacion de Quimica Aplicada Saltillo, Coahuila, Mexico 25253

  19. Recent developments in β-C-glycosides: synthesis and applications.

    PubMed

    Lalitha, Krishnamoorthy; Muthusamy, Kumarasamy; Prasad, Y Siva; Vemula, Praveen Kumar; Nagarajan, Subbiah

    2015-01-30

    In the last few years, considerable progress has been made in the synthesis of C-glycosides. Despite its challenging chemistry, due to its versatility, C-glycosides play a pivotal role in developing novel materials, surfactants and bioactive molecules. In this review, we present snapshots of various synthetic methodologies developed for C-glycosides in the recent years and the potential application of C-glycosides derived from β-C-glycosidic ketones.

  20. 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.

  1. Copper(II)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes.

    PubMed

    Sun, Shutao; Mao, Ying; Lou, Hongxiang; Liu, Lei

    2015-07-07

    The first catalytic asymmetric alkylation of N-acyl quinoliniums with aldehydes has been described. A copper/amine synergistic catalytic system has been developed, allowing the addition of functionalized aldehydes to a wide range of electronically varied N-acyl quinoliniums in good yields with excellent enantiocontrol. The synergistic catalytic system was also effective for N-acyl dihydroisoquinoliniums and β-caboliniums, demonstrating the general applicability of the protocol in the enantioselective alkylation of diverse cyclic N-acyl hemiaminals.

  2. 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.

  3. 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.

  4. 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

  5. Palladium-catalyzed enantioselective 1,1-fluoroarylation of aminoalkenes.

    PubMed

    He, Ying; Yang, Zhenyu; Thornbury, Richard T; Toste, F Dean

    2015-09-30

    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.

  6. 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

  7. 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

  8. 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.

  9. Nanodiamonds of Laser Synthesis for Biomedical Applications.

    PubMed

    Perevedentseva, E; Peer, D; Uvarov, V; Zousman, B; Levinson, O

    2015-02-01

    In recent decade detonation nanodiamonds (DND), discovered 50 years ago and used in diverse technological processes, have been actively applied in biomedical research as a drug and gene delivery carrier, a contrast agent for bio-imaging and diagnostics and an adsorbent for protein separation and purification. In this work we report about nanodiamonds of high purity produced by laser assisted technique, compare them with DND and consider the prospect and advantages of their use in the said applications.

  10. Large Area Graphene Synthesis and its Applications

    DTIC Science & Technology

    2013-12-10

    The University of Texas at Dallas), iii) and utilize them for various applications such as explosive sensor, biofuel cell, Peltier device, organic...relations between two single layer graphenes. Transferred CVD graphene was annealed in the TEM chamber up to 1200ºC to explore the effects that high...resulting nanoribbons show p-type character and field effect GOn/GOff > 104. The results suggest a simple route towards patterning narrow GNR with

  11. Molecularly imprinted materials: synthesis, properties, applications

    NASA Astrophysics Data System (ADS)

    Lisichkin, Georgii V.; Krutyakov, Yu A.

    2006-10-01

    This review is devoted to the method of molecular imprinting. The physicochemical fundamentals and mechanisms of covalent and non-covalent molecular imprinting aimed at the development of organic polymeric sorbents capable of molecular recognition are considered. Attention is focused on the preparation of molecular imprints on mineral supports. The mechanisms of molecular recognition in adsorption are discussed. Application fields of materials with molecular imprints are briefly surveyed.

  12. [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.

  13. 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

  14. Synthesis, characterisation and applications of coiled carbon nanotubes.

    PubMed

    Hanus, Monica J; Harris, Andrew T

    2010-04-01

    Coiled carbon nanotubes are helical carbon structures formed when heptagonal and pentagonal rings are inserted into the hexagonal backbone of a 'straight' nanotube. Coiled carbon nanotubes have been reported with both regular and irregular helical structures. In this work the structure, growth mechanism(s), synthesis, properties and potential applications of coiled carbon nanotubes are reviewed. Published data suggests that coiled carbon nanotube synthesis occurs due to nonuniform extrusion of carbon from a catalyst surface. To date, coiled carbon nanotubes have been synthesised using catalyst modification techniques including: (i) the addition of S or P containing compounds during synthesis; (ii) the use of binary or ternary metal catalysts; (iii) the use of microwaves to create a local temperature gradient around individual catalyst particles and; (iv) the use of pH control during catalyst preparation. In most instances coiled carbon nanotubes are produced as a by-product; high yield and/or large-scale synthesis of coiled carbon nanotubes remains problematic. The qualitative analysis of coiled carbon nanotubes is currently hindered by the absence of specific characterisation data in the literature, e.g., oxidation profiles measured by thermogravimetric analysis and Raman spectra of pure coiled carbon nanotube samples.

  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

    2011-01-07

    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. 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

  17. 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.

  18. 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.

  19. Boron nitride nanotube: synthesis and applications

    NASA Astrophysics Data System (ADS)

    Tiano, Amanda L.; Park, Cheol; Lee, Joseph W.; Luong, Hoa H.; Gibbons, Luke J.; Chu, Sang-Hyon; Applin, Samantha; 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.

    2014-04-01

    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.

  20. 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

  1. Enantioselective quantification of chiral drugs in human plasma with LC-MS/MS.

    PubMed

    Liu, Ke; Zhong, Dafang; Chen, Xiaoyan

    2009-06-01

    Today, approximately 60% of synthetic drugs are chiral and 88% of these chiral synthetic drugs are used therapeutically as racemates. However, for many racemic drugs, their stereospecific plasma pharmacokinetics in humans are not known due to the limitations of the analytical methods. Nowadays, liquid chromatography (LC)-tandem mass spectrometry (MS/MS) methods based on various chiral stationary phases (CSPs), with a high degree of specificity and sensitivity, have been widely used in enantioselective determination of chiral drugs and/or their metabolites in human plasma. The technologies and issues when coupling chiral chromatography with MS/MS detection in bioanalytical methods will be reviewed herein. The introduction and applications of various CPSs, including polysaccharide-, macrocyclic glycopeptide-, protein- and cyclodextrin-based phases, are described here. This review also includes a discussion of interface and matrix effects in enantioselective LC-MS/MS methods.

  2. Enantioselective Trifluoromethylthiolating Lactonization Catalyzed by an Indane-Based Chiral Sulfide.

    PubMed

    Liu, Xiang; An, Rui; Zhang, Xuelin; Luo, Jie; Zhao, Xiaodan

    2016-05-04

    Enantioselective trifluoromethylthiolation, especially of alkenes, is a challenging task. In this work, we have developed an efficient approach for enantioselective trifluoromethylthiolating lactonization by designing an indane-based bifunctional chiral sulfide catalyst and a shelf-stable electrophilic SCF3 reagent. The desired products were formed with diastereoselectivities of >99:1 and good to excellent enantioselectivities. The transformation represents the first enantioselective trifluoromethylthiolation of alkenes and the first enantioselective trifluoromethylthiolation that is enabled by a catalyst with a Lewis basic sulfur center.

  3. 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

  4. Synthesis, properties, and optical applications of low-dimensional perovskites.

    PubMed

    Zhang, Yupeng; Liu, Jingying; Wang, Ziyu; Xue, Yunzhou; Ou, Qingdong; Polavarapu, Lakshminarayana; Zheng, Jialu; Qi, Xiang; Bao, Qiaoliang

    2016-11-17

    Metal-halide perovskites have been hailed as remarkable materials for photovoltaic devices and, recently, their star has also been on the rise in optoelectronics and photonics. In particular, the optical properties of a metal-halide perovskite can be widely manipulated once its bulk structure has been reduced to a low-dimensional structure, allowing multiple functionalities of light generation, emission, transmission, and detection to be realized in one material. In this paper, we highlight the recent advances in the synthesis of low-dimensional metal-halide perovskites and their unique properties as well as their novel optoelectronic and photonic applications. It is anticipated that this review can serve as an overview and evaluation of state-of-the-art synthesis techniques as well as nanoscale optoelectronics and photonics based on low-dimensional perovskite nanocrystals.

  5. Synthesis, Properties, and Applications of Hollow Micro-/Nanostructures.

    PubMed

    Wang, Xiaojing; Feng, Ji; Bai, Yaocai; Zhang, Qiao; Yin, Yadong

    2016-09-28

    In this Review, we aim to provide an updated summary of the research related to hollow micro- and nanostructures, covering both their synthesis and their applications. After a brief introduction to the definition and classification of the hollow micro-/nanostructures, we discuss various synthetic strategies that can be grouped into three major categories, including hard templating, soft templating, and self-templating synthesis. For both hard and soft templating strategies, we focus on how different types of templates are generated and then used for creating hollow structures. At the end of each section, the structural and morphological control over the product is discussed. For the self-templating strategy, we survey a number of unconventional synthetic methods, such as surface-protected etching, Ostwald ripening, the Kirkendall effect, and galvanic replacement. We then discuss the unique properties and niche applications of the hollow structures in diverse fields, including micro-/nanocontainers and reactors, optical properties and applications, magnetic properties, energy storage, catalysis, biomedical applications, environmental remediation, and sensors. Finally, we provide a perspective on future development in the research relevant to hollow micro-/nanostructures.

  6. Bismuth-based oxide semiconductors: Mild synthesis and practical applications

    NASA Astrophysics Data System (ADS)

    Timmaji, Hari Krishna

    In this dissertation study, bismuth based oxide semiconductors were prepared using 'mild' synthesis techniques---electrodeposition and solution combustion synthesis. Potential environmental remediation and solar energy applications of the prepared oxides were evaluated. Bismuth vanadate (BiVO4) was prepared by electrodeposition and solution combustion synthesis. A two step electrosynthesis strategy was developed and demonstrated for the first time. In the first step, a Bi film was first electrodeposited on a Pt substrate from an acidic BiCl3 medium. Then, this film was anodically stripped in a medium containing hydrolyzed vanadium precursor, to generate Bi3+, and subsequent BiVO4 formation by in situ precipitation. The photoelectrochemical data were consistent with the in situ formation of n-type semiconductor films. In the solution combustion synthesis procedure, BiVO4 powders were prepared using bismuth nitrate pentahydrate as the bismuth precursor and either vanadium chloride or vanadium oxysulfate as the vanadium precursor. Urea, glycine, or citric acid was used as the fuel. The effect of the vanadium precursor on the photocatalytic activity of combustion synthesized BiVO 4 was evaluated in this study. Methyl orange was used as a probe to test the photocatalytic attributes of the combustion synthesized (CS) samples, and benchmarked against a commercial bismuth vanadate sample. The CS samples showed superior activity to the commercial benchmark sample, and samples derived from vanadium chloride were superior to vanadium oxysulfate counterparts. The photoelectrochemical properties of the various CS samples were also studied and these samples were shown to be useful both for environmental photocatalytic remediation and water photooxidation applications. Silver bismuth tungstate (AgBiW2O8) nanoparticles were prepared for the first time by solution combustion synthesis by using silver nitrate, bismuth nitrate, sodium tungstate as precursors for Ag, Bi, and W

  7. 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 %.

  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. 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

  10. Enantioselective cellular uptake of chiral semiconductor nanocrystals.

    PubMed

    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

    2016-02-19

    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.

  11. 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

  12. Enantioselective Organocatalytic Cascade Approach to Different Classes of Benzofused Acetals.

    PubMed

    Paz, Bruno Matos; Klier, Lydia; Naesborg, Line; Lauridsen, Vibeke Henriette; Jensen, Frank; Jørgensen, Karl Anker

    2016-11-14

    A novel enantioselective organocatalytic strategy is presented for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine natural product core structures. The strategy is based on a pair of divergent reaction pathways in which hydroxyarenes react with γ-keto-α,β-unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway, which leads to chiral 5,5-fused acetals with two stereocenters-the tetrahydrofurobenzofuran scaffolds-proceeds in moderate yields and up to 96 % ee. The other reaction pathway provides 5,6-bridged methanobenzodioxepine scaffolds with three stereocenters in moderate to good yields and up to 95 % ee. The reaction is remarkable as it can proceed with catalyst loadings as low as 0.25 mol %, providing one of the highest known turnover numbers in iminium ion catalysis. Furthermore, the hemiacetal tetrahydrofurobenzofuran can undergo functionalizations including reduction, oxidation, and allylation. Finally, the effects involved in the substrate control for the divergent pathways, based on both experimental and computational studies, have been investigated. A model involving steric, electronic and stereoelectronic interactions is discussed to rationalize the observed selectivities.

  13. 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.

  14. 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.

  15. Synthesis and functionalisation of magnetic nanoparticles for hyperthermia applications.

    PubMed

    Grüttner, Cordula; Müller, Knut; Teller, Joachim; Westphal, Fritz

    2013-12-01

    A summary of recent developments in the synthesis, stabilisation and coating of magnetic iron oxide nanoparticles for hyperthermia applications is presented. Methods for synthesis in aqueous, organic and microemulsion systems are reviewed together with the resulting heating rates of the nanoparticles. Different stabilisation mechanisms for iron oxide nanoparticles from aqueous and organic media are discussed as intermediates for further coating and functionalisation. Coating with silica and/or polysaccharides is mainly used for design of nanoparticles especially for targeted hyperthermia application. These coatings permit versatile functionalisation as a basis for conjugating biomolecules, e.g. antibodies or peptides. Various strategies to conjugate biomolecules on the particle surface are discussed, with emphasis on methods that preserve biofunctionality after immobilisation. The efficiency of established methods such as carbodiimide coupling and oriented conjugation strategies is compared with new developments such as the bioorthogonal approaches that are based on the cycloaddition of strain-promoted alkynes with azides or nitrones. For targeted hyperthermia applications the study of the formation of a protein corona around nanoparticles with site-specific biomolecules on the surface is essential to achieve improved circulation times in the blood and reduced non-specific uptake by non-targeted organs for a high specific accumulation in the target tissue.

  16. 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.

  17. 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.

  18. Functionalized Gold Nanoparticles: Synthesis, Properties and Applications--A Review.

    PubMed

    Alex, Saji; Tiwari, Ashutosh

    2015-03-01

    The past few decades have witnessed significant advances in the development of functionalized gold nanoparticles for applications in various fields such as chemistry, biology, pharmacy and physics. Although it has been more than 150 years since they were first synthesized, extensive research has recently been undertaken to improve or modify gold nanoparticles, thereby opening up opportunities to enhance and optimize their potential and breadth of their applicability. Recently developed methods have allowed a precise control of gold nanoparticle size and the modification of gold nanoparticles with suitable protecting and functionalizing agents, facilitate their applications in different areas such as chemical and biological sensing, imaging and biomedical applications. This review focuses on the recent developments in various methods for the size and shape controlled synthesis of gold nanoparticles, understanding of different properties of gold nanoparticles and their applications in various fields. Particular attention is given to the chemical and biological sensing applications of gold nanoparticles and on the advances in the controlled ordering of gold nanoparticles for creating nanostructures for diverse applications.

  19. 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

  20. 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.

  1. Cell-free protein synthesis: applications in proteomics and biotechnology.

    PubMed

    He, Mingyue

    2008-01-01

    Protein production is one of the key steps in biotechnology and functional proteomics. Expression of proteins in heterologous hosts (such as in E. coli) is generally lengthy and costly. Cell-free protein synthesis is thus emerging as an attractive alternative. In addition to the simplicity and speed for protein production, cell-free expression allows generation of functional proteins that are difficult to produce by in vivo systems. Recent exploitation of cell-free systems enables novel development of technologies for rapid discovery of proteins with desirable properties from very large libraries. This article reviews the recent development in cell-free systems and their application in the large scale protein analysis.

  2. 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

  3. Novel N-Doped Carbon Dots/β-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers

    PubMed Central

    Xiao, Qi; Lu, Shuangyan; Huang, Chusheng; Su, Wei; Huang, Shan

    2016-01-01

    Based on N-doped carbon dots/β-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/β-CD/GCE), an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp) enantiomers was developed by differential pulse voltammograms (DPVs). Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/β-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C–N bond formation between N-CDs and electrode. The obtained N-CDs/β-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/β-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/β-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/β-CD/GCE combined advantages of N-CDs with strong C–N binding ability and β-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications. PMID:27834863

  4. Novel N-Doped Carbon Dots/β-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers.

    PubMed

    Xiao, Qi; Lu, Shuangyan; Huang, Chusheng; Su, Wei; Huang, Shan

    2016-11-09

    Based on N-doped carbon dots/β-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/β-CD/GCE), an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp) enantiomers was developed by differential pulse voltammograms (DPVs). Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/β-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C-N bond formation between N-CDs and electrode. The obtained N-CDs/β-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/β-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/β-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/β-CD/GCE combined advantages of N-CDs with strong C-N binding ability and β-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications.

  5. Enantioselective construction of remote quaternary stereocentres

    NASA Astrophysics Data System (ADS)

    Mei, Tian-Sheng; Patel, Harshkumar H.; Sigman, Matthew S.

    2014-04-01

    Small molecules that contain all-carbon quaternary stereocentres--carbon atoms bonded to four distinct carbon substituents--are found in many secondary metabolites and some pharmaceutical agents. The construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for synthesizing quaternary stereocentres that are remote from other functional groups are underdeveloped. Here we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids. This method provides direct access to quaternary all-carbon-substituted β-, γ-, δ-, ɛ- or ζ-aryl carbonyl compounds, because 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 stereocentres along the alkyl chain, which links the alkene and the alcohol, in which the stereocentre is preserved. The method described allows access to diverse molecular building blocks containing an enantiomerically enriched quaternary centre.

  6. 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

  7. 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.

  8. A Concise Asymmetric Total Synthesis of (+)-Brevisamide

    PubMed Central

    Herrmann, Aaron T.; Martinez, Steven R.; Zakarian, Armen

    2012-01-01

    A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide. PMID:21678904

  9. 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.

  10. 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.

  11. Luminescent metal nanoclusters: controlled synthesis and functional applications

    PubMed Central

    Sun, Hong-Tao; Sakka, Yoshio

    2014-01-01

    Luminescent metal nanoclusters that consist of only several, to tens of, metal atoms and which possess sizes comparable to the Fermi wavelength of electrons have recently attracted significant attention. This new class of luminescent materials not only provides the missing link between atomic and nanoparticle behaviors in metals but also they present abundant novel information for the development of new applicable material systems to meet urgent needs in many areas (such as ultrasensitive sensors for heavy metals, bioimaging, as well as information technology) mainly because of their attractive characteristics, including ultra-small size, good dispersibility, excellent biocompatibility and photostability. In this review, we summarize recent advances in the controlled synthesis and application of luminescent metal nanoclusters, with a particular emphasis on Pt, Mo, Bi and alloy clusters. We also speculate on their future and discuss potential developments for their use in sensors, bioimaging and energy harvesting and conversion. PMID:27877632

  12. Graphene-based materials: synthesis, characterization, properties, and applications.

    PubMed

    Huang, Xiao; Yin, Zongyou; Wu, Shixin; Qi, Xiaoying; He, Qiyuan; Zhang, Qichun; Yan, Qingyu; Boey, Freddy; Zhang, Hua

    2011-07-18

    Graphene, a two-dimensional, single-layer sheet of sp(2) hybridized carbon atoms, has attracted tremendous attention and research interest, owing to its exceptional physical properties, such as high electronic conductivity, good thermal stability, and excellent mechanical strength. Other forms of graphene-related materials, including graphene oxide, reduced graphene oxide, and exfoliated graphite, have been reliably produced in large scale. The promising properties together with the ease of processibility and functionalization make graphene-based materials ideal candidates for incorporation into a variety of functional materials. Importantly, graphene and its derivatives have been explored in a wide range of applications, such as electronic and photonic devices, clean energy, and sensors. In this review, after a general introduction to graphene and its derivatives, the synthesis, characterization, properties, and applications of graphene-based materials are discussed.

  13. Upconversion Nanoparticles: Synthesis, Surface Modification, and Biological Applications

    PubMed Central

    Wang, Meng; Abbineni, Gopal; Clevenger, April; Mao, Chuanbin; Xu, Shukun

    2011-01-01

    New generation fluorophores, also termed upconversion nanoparticles (UCNPs), have the ability to convert near infrared radiations with lower energy into visible radiations with higher energy via a non-linear optical process. Recently, these UCNPs have evolved as alternative fluorescent labels to traditional fluorophores, showing great potential for imaging and biodetection assays in both in vitro and in vivo applications. UCNPs exhibit unique luminescent properties, including high penetration depth into tissues, low background signals, large Stokes shifts, sharp emission bands, and high resistance to photo-bleaching, making UCNPs an attractive alternative source for overcoming current limitations in traditional fluorescent probes. In this review, we discuss the recent progress in the synthesis and surface modification of rare earth doped UCNPs with a specific focus on their biological applications. PMID:21419877

  14. Enantioselective bioconversion using Escherichia coli cells expressing Saccharomyces cerevisiae reductase and Bacillus subtilis glucose dehydrogenase.

    PubMed

    Park, Hyun Joo; Jung, Jihye; Choi, Hyejeong; Uhm, Ki-Nam; Kim, Hyung Kwoun

    2010-09-01

    Ethyl (R, S)-4-chloro-3-hydroxybutanoate (ECHB) is a useful chiral building block for the synthesis of L-carnitine and hypercholesterolemia drugs. The yeast reductase, YOL151W (GenBank locus tag), exhibits an enantioselective reduction activity, converting ethyl-4-chlorooxobutanoate (ECOB) exclusively into (R)-ECHB. YOL151W was generated in Escherichia coli cells and purified via Ni- NTA and desalting column chromatography. It evidenced an optimum temperature of 45 degrees C and an optimum pH of 6.5-7.5. Bacillus subtilis glucose dehydrogenase (GDH) was also expressed in Escherichia coli, and was used for the recycling of NADPH, required for the reduction reaction. Thereafter, Escherichia coli cells co-expressing YOL151W and GDH were constructed. After permeablization treatment, the Escherichia coli whole cells were utilized for ECHB synthesis. Through the use of this system, the 30 mM ECOB substrate could be converted to (R)-ECHB.

  15. Virtual Issue: Carbohydrates in the 21(st) Century: Synthesis and Applications.

    PubMed

    Fairbanks, Antony J

    2015-12-01

    Creative with carbohydrates! This Virtual Issue on Carbohydrates in the 21 (st) Century: Synthesis and Applications highlights current research in the carbohydrate field in which synthesis underpins the development of novel applications of sugar-based materials in medicine, diagnostics, and as antiinfectives.

  16. 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.

  17. Enantioselective effects of herbicide imazapyr on Arabidopsis thaliana.

    PubMed

    Hsiao, Yu-Ling; Wang, Yei-Shung; Yen, Jui-Hung

    2014-01-01

    The enantioselective toxicity of chiral herbicides in the environment is of increasing concern. To investigate the enantioselective effects of the chiral herbicide imazapyr on target organisms, we exposed Arabidopsis thaliana to imazapyr enantiomers and racemate. The results show that imazapyr was enantioselectively toxic to A. thaliana. The total chlorophyll content in A. thaliana was affected more by (+)-imazapyr than (±)-imazapyr and (-)-imazapyr. Concentrations of proline and malondialdehyde reflected a toxic effect in the order of (+)-imazapyr > (±)-imazapyr > (-)-imazapyr at every concentration. Acetolactate synthase (ALS) activity was inhibited more by (+)-imazapyr than (±)-imazapyr or (-)-imazapyr. At 100 mg L(-1) of imazapyr, ALS activity was 78%, 43%, and 19% with (-)-, (±)-, and (+)-imazapyr, respectively. The results suggest the significant enantioselective toxicity of imazapyr in A. thaliana for greater toxicity with (+)-imazapyr than (±)-imazapyr and (-)-imazapyr, which suggests that (+)-imazapyr has more herbicidal effect.

  18. A general enantioselective route to the chamigrene natural product family

    PubMed Central

    White, David E.; Stewart, Ian C.; Seashore-Ludlow, Brinton A.; Grubbs, Robert H.; Stoltz, Brian M.

    2010-01-01

    Described in this report is an enantioselective route toward the chamigrene natural product family. The key disconnections in our synthetic approach include sequential enantioselective decarboxylative allylation and ring-closing olefin metathesis to form the all-carbon quaternary stereocenter and spirocyclic core present in all members of this class of compounds. The generality of this strategy is demonstrated by the first total syntheses of elatol and the proposed structure of laurencenone B, as well as the first enantioselective total syntheses of laurencenone C and α-chamigrene. A brief exploration of the substrate scope of the enantioselective decarboxylative allylation/ring-closing metathesis sequence with fully substituted vinyl chlorides is also presented. PMID:20798895

  19. Cyclic sulfamidates as lactam precursors. An efficient asymmetric synthesis of (-)-aphanorphine.

    PubMed

    Bower, John F; Szeto, Peter; Gallagher, Timothy

    2005-12-14

    A short and efficient enantioselective synthesis of (-)-aphanorphine is described based on the use of a cyclic sulfamidate to provide a suitably functionalised lactam that allows for construction of the tricyclic 3-benzazepine scaffold.

  20. Catalytic Kinetic Resolution of Saturated N-Heterocycles by Enantioselective Amidation with Chiral Hydroxamic Acids.

    PubMed

    Kreituss, Imants; Bode, Jeffrey W

    2016-12-20

    The preparation of enantioenriched chiral compounds by kinetic resolution dates back to the laboratories of Louis Pasteur in the middle of the 19th century. Unlike asymmetric synthesis, this process can always deliver enantiopure material (ee > 99%) if the reactions are allowed to proceed to sufficient conversion and the selectivity of the process is not unity (s > 1). One of the most appealing and practical variants is acylative kinetic resolution, which affords easily separable reaction products, and several highly efficient enzymatic and small molecule catalysts are available. Unfortunately, this method is applicable to limited substrate classes such as alcohols and primary benzylamines. This Account focuses on our work in catalytic acylative kinetic resolution of saturated N-heterocycles, a class of molecules that has been notoriously difficult to access via asymmetric synthesis. We document the development of hydroxamic acids as suitable catalysts for enantioselective acylation of amines through relay catalysis. Alongside catalyst optimization and reaction development, we present mechanistic studies and theoretical calculation accounting for the origins of selectivity and revealing the concerted nature of many amide-bond forming reactions. Immobilization of the hydroxamic acid to form a polymer supported reagent allows simplification of the experimental setup, improvement in product purification, and extension of the substrate scope. The kinetic resolutions are operationally straight forward: reactions proceed at room temperature and open to air conditions, without generation of difficult-to-remove side products. This was utilized to achieve decagram scale resolution of antimalarial drug mefloquine to prepare more than 50 g of (+)-erythro-meflqouine (er > 99:1) from the racemate. The immobilized quasienantiomeric acyl hydroxamic acid reagents were also exploited for a rare practical implementation of parallel kinetic resolution that affords both enantiomers of

  1. 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

  2. Enantioselective Dearomative [3+2] Cycloaddition Reactions of Benzothiazoles.

    PubMed

    Wang, Dong-Chao; Xie, Ming-Sheng; Guo, Hai-Ming; Qu, Gui-Rong; Zhang, Meng-Cheng; You, Shu-Li

    2016-11-02

    A highly enantioselective dearomative [3+2] cycloaddition of benzothiazole has been successfully developed. A wide range of benzothiazoles and cyclopropane-1,1-dicarboxylates are suitable substrates for this reaction. The desired hydropyrrolo[2,1-b]thiazole compounds were obtained in excellent enantioselectivity and yields (up to 97 % ee and 97 % yield). With the same catalytic system, a highly efficient kinetic resolution of 2-substituted cyclopropane-1,1-dicarboxylates was also realized.

  3. Applications of ultrasound to the synthesis of nanostructured materials.

    PubMed

    Bang, Jin Ho; Suslick, Kenneth S

    2010-03-12

    Recent advances in nanostructured materials have been led by the development of new synthetic methods that provide control over size, morphology, and nano/microstructure. The utilization of high intensity ultrasound offers a facile, versatile synthetic tool for nanostructured materials that are often unavailable by conventional methods. The primary physical phenomena associated with ultrasound that are relevant to materials synthesis are cavitation and nebulization. Acoustic cavitation (the formation, growth, and implosive collapse of bubbles in a liquid) creates extreme conditions inside the collapsing bubble and serves as the origin of most sonochemical phenomena in liquids or liquid-solid slurries. Nebulization (the creation of mist from ultrasound passing through a liquid and impinging on a liquid-gas interface) is the basis for ultrasonic spray pyrolysis (USP) with subsequent reactions occurring in the heated droplets of the mist. In both cases, we have examples of phase-separated attoliter microreactors: for sonochemistry, it is a hot gas inside bubbles isolated from one another in a liquid, while for USP it is hot droplets isolated from one another in a gas. Cavitation-induced sonochemistry provides a unique interaction between energy and matter, with hot spots inside the bubbles of approximately 5000 K, pressures of approximately 1000 bar, heating and cooling rates of >10(10) K s(-1); these extraordinary conditions permit access to a range of chemical reaction space normally not accessible, which allows for the synthesis of a wide variety of unusual nanostructured materials. Complementary to cavitational chemistry, the microdroplet reactors created by USP facilitate the formation of a wide range of nanocomposites. In this review, we summarize the fundamental principles of both synthetic methods and recent development in the applications of ultrasound in nanostructured materials synthesis.

  4. Carbon nanotubes and tungsten oxide nanorods: Synthesis and applications

    NASA Astrophysics Data System (ADS)

    Xiao, Bing

    Synthesis and applications of two types of one-dimensional nanomaterials, carbon nanotubes (CNTs) and tungsten oxide nanorods, are investigated in this dissertation. Multi-walled CNTs have been successfully synthesized using two types of chemical vapor deposition (CVD) methods: microwave plasma enhanced CVD and atmospheric pressure thermal CVD. CNTs and their synthesis processes are characterized with various analysis techniques including scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, and optical emission spectroscopy. Ultra-thin and high quality multi-walled CNTs are discovered in CNT films produced by MPCVD, which exhibit good field emission performance that is found to be dependent on the synthesis conditions, like the growth time and CH4/H2 flow ratio. CNTs grown by thermal CVD have similar field emission performance. Based on silicon surface micromachining techniques and thermal CVD method, a self-aligned method has been developed to fabricate CNT based gated field emitter arrays (FEAs) which demonstrate low turn-on voltage and good emission current. Tungsten oxide nanorods have been synthesized on various tungsten substrates via thermal annealing in argon at atmospheric pressure. Nanorod growth mechanism is proposed based on thermal oxidation of tungsten in gas ambient with a very low partial pressure of oxygen as well as the self-catalytic effect on tungsten surface. The lattice structure and composition of the tungsten oxide nanorods are observed and analyzed using high resolution TEM, selected area electron diffraction (SAD), and energy dispersive X-ray spectroscopy (EDXS). The analysis results reveal that the lattice structure of the tungsten oxide nanorods is closest to that of the monoclinic WO3 crystal. Tungsten oxide nanorods have been successfully grown on tungsten tips for use in scanning tunneling microscope (STM) as probes which readily produce atomic resolution images on sample surface. Nanorod

  5. Quadratic optimal cooperative control synthesis with flight control application

    NASA Technical Reports Server (NTRS)

    Schmidt, D. K.; Innocenti, M.

    1984-01-01

    An optimal control-law synthesis approach is presented that involves simultaneous solution for two cooperating controllers operating in parallel. One controller's structure includes stochastic state estimation and linear feedback of the state estimates, while the other controller involves direct linear feedback of selected system output measurements. This structure is shown to be optimal under the constraint of linear feedback of system outputs in one controller. Furthermore, it is appropriate for flight control synthesis where the full-state optimal stochastic controller can be adjusted to be representative of an optimal control model of the human pilot in a stochastic regulation task. The method is experimentally verified in the case of the selection of pitch-damper gain for optimum pitch tracking, where optimum implies the best subjective pilot rating in the task. Finally, results from application of the method to synthesize a controller for a multivariable fighter aircraft are presented, and implications of the results of this method regarding the optimal plant dynamics for tracking are discussed.

  6. Application of Biocatalysis to on-DNA Carbohydrate Library Synthesis.

    PubMed

    Thomas, Baptiste; Lu, Xiaojie; Birmingham, William R; Huang, Kun; Both, Peter; Reyes Martinez, Juana Elizabeth; Young, Robert J; Davie, Christopher P; Flitsch, Sabine L

    2017-01-26

    DNA-encoded libraries are increasingly used for the discovery of bioactive lead compounds in high-throughput screening programs against specific biological targets. Although a number of libraries are now available, they cover limited chemical space due to bias in ease of synthesis and the lack of chemical reactions that are compatible with DNA tagging. For example, compound libraries rarely contain complex biomolecules such as carbohydrates with high levels of functionality, stereochemistry, and hydrophilicity. By using biocatalysis in combination with chemical methods, we aimed to significantly expand chemical space and generate generic libraries with potentially better biocompatibility. For DNA-encoded libraries, biocatalysis is particularly advantageous, as it is highly selective and can be performed in aqueous environments, which is an essential feature for this split-and-mix library technology. In this work, we demonstrated the application of biocatalysis for the on-DNA synthesis of carbohydrate-based libraries by using enzymatic oxidation and glycosylation in combination with traditional organic chemistry.

  7. Application of response surface methodology in enzymatic synthesis: a review.

    PubMed

    Ghaffari-Moghaddam, Mansour; Yekke-Ghasemi, Zahra; Khajeh, Mostafa; Rakhshanipour, Mansoureh; Yasin, Yamin

    2014-01-01

    There are very chemical reactions with very slow rates which can be catalyzed by enzymes. These biocatalysts need to moderate conditions for their catalytic activity and are stable in low temperature (between 15-50°C), average pH (5-10) and aqueous media. One of important things in enzymatic synthesis which has been recently noticed is the yield of reactions. Nowadays wide application of response surface methodology (RSM) was observed in organic chemistry. In one-variable-at-a-time technique only one parameter is changed and other parameters are kept at a constant level. It does not study the interactive effects among the variables, and does not illustrate the complete effects of the parameters on the process. Increasing the yield of product without increase in casts is carried out by modeling and optimization of reaction variables through statistical techniques such as RSM. In this paper, we reviewed some articles that used the RSM for optimization in the enzymatic synthesis.

  8. 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.

  9. Ni(II)-Bis[(R,R)-N,N'-dibenzylcyclohexane-1,2-diamine]Br2 catalyzed enantioselective Michael additions of 1,3-dicarbonyl compounds to conjugated nitroalkenes.

    PubMed

    Evans, David A; Seidel, Daniel

    2005-07-20

    A highly enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes has been developed that employs a newly developed Ni(II)-(bis)diamine based catalyst. The reaction scope includes substituted and unsubstituted malonates, beta-ketoesters, and nitroalkenes bearing aromatic and aliphatic residues. Ease of synthesis of this complex is noteworthy.

  10. Catalytic enantioselective amination of alcohols by the use of borrowing hydrogen methodology: cooperative catalysis by iridium and a chiral phosphoric acid.

    PubMed

    Zhang, Yao; Lim, Ching-Si; Sim, Derek Sui Boon; Pan, Hui-Jie; Zhao, Yu

    2014-01-27

    The catalytic asymmetric reduction of ketimines has been explored extensively for the synthesis of chiral amines, with reductants ranging from Hantzsch esters, silanes, and formic acid to H2 gas. Alternatively, the amination of alcohols by the use of borrowing hydrogen methodology has proven a highly atom economical and green method for the production of amines without an external reductant, as the alcohol substrate serves as the H2 donor. A catalytic enantioselective variant of this process for the synthesis of chiral amines, however, was not known. We have examined various transition-metal complexes supported by chiral ligands known for asymmetric hydrogenation reactions, in combination with chiral Brønsted acids, which proved essential for the formation of the imine intermediate and the transfer-hydrogenation step. Our studies led to an asymmetric amination of alcohols to provide access to a wide range of chiral amines with good to excellent enantioselectivity.

  11. Framed carbon nanostructures: synthesis and applications in functional SPM tips.

    PubMed

    Mukhin, I S; Fadeev, I V; Zhukov, M V; Dubrovskii, V G; Golubok, A O

    2015-01-01

    We present a synthesis method to fabricate framed carbon-based nanostructures having highly anisotropic shapes, in particular, the nanofork and nanoscalpel structures which are obtained systematically under optimized growth conditions. A theoretical model is developed to explain the formation of such nanostructures on Si cantilevers and W etched wires exposed to a focused electron beam. We then demonstrate the potentials of these nanostructures as functional tips for scanning probe microscopy. Owing to their anisotropic shapes, such tips can be very useful for nanolithography, nanosurgery of biological objects, and precise manipulation with surface particles. Overall, our method provides a simple and robust way to produce functional scanning probe microscopy tips with variable shapes and enhanced capabilities for different applications compared to standard cantilevers.

  12. One-dimensional boron nanostructures: Prediction, synthesis, characterizations, and applications.

    PubMed

    Tian, Jifa; Xu, Zhichuan; Shen, Chengmin; Liu, Fei; Xu, Ningsheng; Gao, Hong-Jun

    2010-08-01

    One-dimensional (1D) boron nanostructures are very potential for nanoscale electronic devices since their physical properties including electric transport and field emission have been found very promising as compared to other well-developed 1D nanomaterials. In this article, we review the current progress that has been made on 1D boron nanostructures in terms of theoretical prediction, synthetic techniques, characterizations and potential applications. To date, the synthesis of 1D boron nanostructures has been well-developed. The popular structures include nanowires, nanobelts, and nanocones. Some of these 1D nanostructures exhibited improved electric transport properties over bulk boron materials as well as promising field emission properties. By current experimental findings, 1D boron nanostructures are promising to be one of core materials for future nanodevices. More efforts are expected to be made in future on the controlled growth of 1D boron nanostructures and tailoring their physical properties.

  13. Magnetic quantum dots in biotechnology--synthesis and applications.

    PubMed

    Mahajan, Kalpesh D; Fan, Qirui; Dorcéna, Jenny; Ruan, Gang; Winter, Jessica O

    2013-12-01

    Quantum dots (QDs) have great promise in biological imaging, and as this promise is realized, there has been increasing interest in combining the benefits of QDs with those of other materials to yield composites with multifunctional properties. One of the most common materials combined with QDs is magnetic materials, either as ions (e.g. gadolinium) or as nanoparticles (e.g. superparamagnetic iron oxide nanoparticles, SPIONs). The fluorescent property of the QDs permits visualization, whereas the magnetic property of the composite enables imaging, magnetic separation, and may even have therapeutic benefit. In this review, the synthesis of fluorescent-magnetic nanoparticles, including magnetic QDs is explored; and the applications of these materials in imaging, separations, and theranostics are discussed. As the properties of these materials continue to improve, QDs have the potential to greatly impact biological imaging, diagnostics, and treatment.

  14. Hollow magnetic nanoparticles: synthesis and applications in biomedicine.

    PubMed

    He, Quanguo; Wu, Zhaohui; Huang, Chunyan

    2012-04-01

    Magnetic hollow particles (MHP) are widely used in biomedicine field due to their biocompatibility, low-toxicity, low-density and the large fraction void space in the MHP, which have been successfully used to encapsulate and control drugs release, and magnetic resonance imaging (MRI). This review focuses on all kinds of MHP preparation method, compares the advantages and disadvantages in the process of synthesis, and introduces especially the special formation mechanisms such as the Kirkendall effect and Ostwald ripening. Both the compatible interior space and good magnetism of magnetic hollow structures enable them promising and unique candidates as biomedicine vehicles. Particularly, the progress of MHP widely used in the biomedical engineering applications containing drug delivery and magnetic resonance imaging are described. The main problems and the directions in the future researches are pointed out.

  15. 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

  16. 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

  17. Expanding the scope of Metal-Free enantioselective allylic substitutions: Anthrones

    NASA Astrophysics Data System (ADS)

    Ceban, Victor; Tauchman, Jiří; Meazza, Marta; Gallagher, Greg; Light, Mark E.; Gergelitsová, Ivana; Veselý, Jan; Rios, Ramon

    2015-11-01

    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.

  18. Physical Interpretation of Neugebauer Equations and Applications for Achromatic Synthesis

    NASA Astrophysics Data System (ADS)

    Kita, Shinji

    1990-06-01

    As Lambert-Beer's Law in density modulation images, Neugebauer Equations are the basic equation for color reproduction of dot modulation images. Its significance increases with the advance of digital color printing technology. Its' applications have been diversely enlarging to identify the relationship between dot allocation and color gamut', to forecast reproduced color2, and to discuss the achromatic synthesis in principle3, 4. As well known, its principle is that "color is reproduced by averaging additive color mixture of basic 8 colors' area and stimulus determined statistically by the Demichel's law" . The significant assumption here is "the independency of each color area", that is, the coverage and color stimulus of each color area are not influenced by those of neighbor. However, in an actual dot modulation image, optical diffusion and mixture occur within image as known as Yule-Nielsen's effect (Y-N effect). Therefore, the former assumption cannot be adapted on actual images. Since various marking technologies have their own optical diffusion and mixture respectively due to their marking principle and image structure, it seems that an overall comprehension for color reproduction of these images is required from these technologies. And besides, reconstruction of color reproduction theory including density modulation images will be more necessary in future. For this purpose, new theoretical approach adding Y-N effect to Neugebauer equations might be indispensable . From the viewpoint, this paper introduces the full-color image structure models which quantifies optical diffusion and mixture within recorded image and mentions the physical interpretation of Y-N effect in full-color image. Next, by using Neugebauer equations with Y-N effect6, we analyze the achromatic synthesis and propose the theoretical method for black determination applicable to all image formation, through density modulation to completely binary image.

  19. 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

  20. 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

  1. 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

  2. Triaziflam and Diaminotriazine derivatives affect enantioselectively multiple herbicide target sites.

    PubMed

    Grossmann, K; Tresch, S; Plath, P

    2001-01-01

    Enantiomers of triaziflam and structurally related diaminotriazines were synthesized and their herbicidal mode of action was investigated. The compounds caused light and dark-dependent effects in multiple test systems including heterotrophic cleaver and photoautotrophic algal cell suspensions, the Hill reaction of isolated thylakoids and germinating cress seeds. Dose-response experiments revealed that the (S)-enantiomers of the compounds preferentially inhibited photosystem II electron transport (PET) and algae growth with efficacies similar to that of the herbicide atrazine. In contrast, the (R)-enantiomers of the diaminotriazines were up to 100 times more potent inhibitors of growth in cleaver cell suspensions and cress seedlings in the dark than the (S)-enantiomers. The most active compound, the (R)-enantiomer of triaziflam, inhibited shoot and root elongation of cress and maize seedlings at concentrations below 1 microM. The meristematic root tips swelled into a club shape which is typical for the action of mitotic disrupter herbicides and cellulose biosynthesis inhibitors. Microscopic examination using histochemical techniques revealed that triaziflam (R)-enantiomer blocks cell division in maize root tips 4 h after treatment. The chromosomes proceeded to a condensed state of prometaphase but were unable to progress further in the mitotic cycle. Disruption of mitosis was accompanied by a loss of spindle and phragmoplast micotubule arrays. Concomitantly, cortical microtubules decreased which could lead to isodiametric cell growth and consequently to root swelling. In addition, a decline in cellulose deposition in cell walls was found 24 h after treatment. Compared to the (R)-form, triaziflam (S)-enantiomer was clearly less active. The results suggest that triaziflam and related diaminotriazines affect enantioselectively multiple sites of action which include PET inhibitory activity, mitotic disruption by inhibiting microtubule formation and inhibition of

  3. 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.

  4. An NHC-catalyzed in situ activation strategy to β-functionalize saturated carboxylic acid: an enantioselective formal [3+2] annulation for spirocyclic oxindolo-γ-butyrolactones.

    PubMed

    Xie, Yuanwei; Yu, Chenxia; Li, Tuanjie; Tu, Shujiang; Yao, Changsheng

    2015-03-27

    An in situ NHC-catalyzed activation strategy to β-functionalize saturated carboxylic acid was developed. This asymmetric formal [3+2] annulation could deliver spirocyclic oxindolo-γ-butyrolactones from saturated carboxylic acid and isatin in good yields with high to excellent enantioselectivities. The easy availability of the starting materials, direct installation of functional units at unreactive carbon atom and the convergent assembly make this protocol attractive in the field of organic synthesis.

  5. The upside of downsizing: asymmetric trifunctional organocatalysts as small enzyme mimics for cooperative enhancement of both rate and enantioselectivity with regulation.

    PubMed

    Liu, Fei

    2013-11-01

    Small molecule organic catalysts (organocatalysts) are widely used in asymmetric catalysis and synthesis. Compared to their enzymatic and transition-metal counterparts, organocatalysts have advantages in catalytic scope and efficiency but are more limited in proficiency. Chiral trifunctional organocatalysts, in which multiple catalytic motifs act cooperatively on a chiral scaffold, are an emerging class of organocatalysts with improved proficiency. Cooperativity design that enables both enantioselectivity and rate enhancement is essential to developing future generations of organocatalysts in biomimetic asymmetric catalysis.

  6. Gas-phase synthesis of semiconductor nanocrystals and its applications

    NASA Astrophysics Data System (ADS)

    Mandal, Rajib

    Luminescent nanomaterials is a newly emerging field that provides challenges not only to fundamental research but also to innovative technology in several areas such as electronics, photonics, nanotechnology, display, lighting, biomedical engineering and environmental control. These nanomaterials come in various forms, shapes and comprises of semiconductors, metals, oxides, and inorganic and organic polymers. Most importantly, these luminescent nanomaterials can have different properties owing to their size as compared to their bulk counterparts. Here we describe the use of plasmas in synthesis, modification, and deposition of semiconductor nanomaterials for luminescence applications. Nanocrystalline silicon is widely known as an efficient and tunable optical emitter and is attracting great interest for applications in several areas. To date, however, luminescent silicon nanocrystals (NCs) have been used exclusively in traditional rigid devices. For the field to advance towards new and versatile applications for nanocrystal-based devices, there is a need to investigate whether these NCs can be used in flexible and stretchable devices. We show how the optical and structural/morphological properties of plasma-synthesized silicon nanocrystals (Si NCs) change when they are deposited on stretchable substrates made of polydimethylsiloxane (PDMS). Synthesis of these NCs was performed in a nonthermal, low-pressure gas phase plasma reactor. To our knowledge, this is the first demonstration of direct deposition of NCs onto stretchable substrates. Additionally, in order to prevent oxidation and enhance the luminescence properties, a silicon nitride shell was grown around Si NCs. We have demonstrated surface nitridation of Si NCs in a single step process using non?thermal plasma in several schemes including a novel dual-plasma synthesis/shell growth process. These coated NCs exhibit SiNx shells with composition depending on process parameters. While measurements including

  7. Solution synthesis, optical properties, and bioimaging applications of silicon nanocrystals.

    PubMed

    McVey, Benjamin F P; Tilley, Richard D

    2014-10-21

    Understanding and unlocking the potential of semiconductor nanocrystals (NCs) is important for future applications ranging from biomedical imaging contrast agents to the next generation of solar cells and LEDs. Silicon NCs (Si NCs) have key advantages compared with other semiconductor NCs due to silicon's high natural abundance, low toxicity and strong biocompatibility, and unique size, and surface dependent optical properties. In this Account, we review and discuss the synthesis, surface modification, purification, optical properties, and applications of Si NCs. The synthetic methods used to make Si NCs have improved considerably in the last 5-10 years; highly monodisperse Si NCs can now be produced on the near gram scale. Scaled-up syntheses have allowed scientists to drive further toward the commercial utilization of Si NCs. The synthesis of doped Si NCs, through addition of a simple elemental precursor to a reaction mixture or by the production of a single source precursor, has shown great promise. Doped Si NCs have demonstrated unique or enhanced properties compared with pure Si NCs, for example, magnetism due to the presence of magnetic metals like Fe and Mn. Surface reactions have reached a new level of sophistication where organic (epoxidation and diol formation) and click (thiol based) chemical reactions can be carried out on attached surface molecules. This has led to a wide range of biocompatible functional groups as well as a degree of emission tuneability. The purification of Si NCs has been improved through the use of size separation columns and size selective precipitation. These purification approaches have yielded highly monodisperse and pure Si NCs previously unachieved. This has allowed scientists to study the size and surface dependent properties and toxicity and enabled the use of Si NCs in biomedical applications. The optical properties of Si NCs are complex. Using a combination of characterization techniques, researchers have explored the

  8. Co(III)(salen)-catalyzed phenolic kinetic resolution of two stereocentered benzyloxy and azido epoxides: its application in the synthesis of ICI-118,551, an anti-hypertensive agent.

    PubMed

    Karabal, Pratibha U; Kamble, Dayanand A; Sudalai, Arumugam

    2014-04-21

    The salen Co(III)-catalyzed phenolic kinetic resolution of racemic anti- or syn-azido and benzyloxy epoxides provides a practical route to a range of enantioenriched anti- or syn-1-aryloxy-3-azido or benzyloxy-2-alcohols in excellent yields and ees. The synthetic potential of this protocol is illustrated with an enantioselective synthesis of ICI-118,551, a β-blocker, in a highly optically pure form (99% ee).

  9. Epi-cinchona based thiourea organocatalyst family as an efficient asymmetric Michael addition promoter: enantioselective conjugate addition of nitroalkanes to chalcones and alpha,beta-unsaturated N-acylpyrroles.

    PubMed

    Vakulya, Benedek; Varga, Szilárd; Soós, Tibor

    2008-05-02

    A small set of easily available epi-cinchona based thiourea organocatalysts have been synthesized and tested in enantioselective Michael addition of nitroalkanes to chalcones. These bifunctional catalyst systems promoted the conjugate additions with high enantioselectivities and chemical yields. The extension of this methodology was further explored to encompass alpha,beta-unsaturated N-acylpyrroles, as a chalcone mimic. Functionally, the N-acylpyrrole moiety in the adduct acts as an ester surrogate; therefore, it can easily be transformed to various valuable and biologically relevant compounds. This approach allowed the concise stereoselective synthesis of (R)-rolipram.

  10. 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.

  11. Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry: Application to the analysis of drug-drug interaction.

    PubMed

    Liu, Yijin; Jann, Michael; Vandenberg, Chad; Eap, Chin B; Shamsi, Shahab A

    2015-11-13

    To-date, there has been no effective chiral capillary electrophoresis-mass spectrometry (CE-MS) method reported for the simultaneous enantioseparation of the antidepressant drug, venlafaxine (VX) and its structurally-similar major metabolite, O-desmethylvenlafaxine (O-DVX). This is mainly due to the difficulty of identifying MS compatible chiral selector, which could provide both high enantioselectivity and sensitive MS detection. In this work, poly-sodium N-undecenoyl-L,L-leucylalaninate (poly-L,L-SULA) was employed as a chiral selector after screening several dipeptide polymeric chiral surfactants. Baseline separation of both O-DVX and VX enantiomers was achieved in 15 min after optimizing the buffer pH, poly-L,L-SULA concentration, nebulizer pressure and separation voltage. Calibration curves in spiked plasma (recoveries higher than 80%) were linear over the concentration range 150-5000 ng/mL for both VX and O-DVX. The limit of detection (LOD) was found to be as low as 30 ng/mL and 21 ng/mL for O-DVX and VX, respectively. This method was successfully applied to measure the plasma concentrations of human volunteers receiving VX or O-DVX orally when co-administered without and with indinivar therapy. The results suggest that micellar electrokinetic chromatography electrospray ionization-tandem mass spectrometry (MEKC-ESI-MS/MS) is an effective low cost alternative technique for the pharmacokinetics and pharmacodynamics studies of both O-DVX and VX enantiomers. The technique has potential to identify drug-drug interaction involving VX and O-DVX enantiomers while administering indinivar therapy.

  12. Development of an enantioselective assay for simultaneous separation of venlafaxine and O-desmethylvenlafaxine by micellar electrokinetic chromatography-tandem mass spectrometry: Application to the analysis of drug-drug interaction

    PubMed Central

    Liu, Yijin; Jann, Michael; Vandenberg, Chad; Eap, Chin B.; A.Shamsi, Shahab

    2016-01-01

    To-date, there has been no effective chiral capillary electrophoresis-mass spectrometry (CE-MS) method reported for the simultaneous enantioseparation of the antidepressant drug, venlafaxine (VX) and its structurally-similar major metabolite, O-desmethylvenlafaxine (O-DVX). This is mainly due to the difficulty of identifying MS compatible chiral selector, which could provide both high enantioselectivity and sensitive MS detection. In this work, poly-sodium N-undecenoyl-L,L-leucylalaninate (poly-L,L-SULA) was employed as a chiral selector after screening several dipeptide polymeric chiral surfactants. Baseline separation of both O-DVX and VX enantiomers was achieved in 15 min after optimizing the buffer pH, poly-L L-SULA concentration, nebulizer pressure and separation voltage. Calibration curves in spiked plasma (recoveries higher than 80%) were linear over the concentration range 150–5,000 ng/mL for both VX and O-DVX. The limit of detection (LOD) was found to be as low as 30 ng/mL and 21 ng/mL for O-DVX and VX, respectively. This method was successfully applied to measure the plasma concentrations of human volunteers receiving VX or O-DVX orally when co-administered without and with indinivar therapy. The results suggest that micellar electrokinetic chromatography electrospray ionization-tandem mass spectrometry (MEKC-ESI-MS/MS) is an effective low cost alternative technique for the pharmacokinetics and pharmacodynamics studies of both O-DVX and VX enantiomers. The technique has potential to identify drug-drug interaction involving VX and O-DVX enantiomers while administering indinivar therapy. PMID:26460073

  13. 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

    2015-10-05

    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.

  14. Synthesis of internally functionalized silica nanoparticles for theranostic applications

    NASA Astrophysics Data System (ADS)

    Walton, Nathan Isaac

    This thesis addresses the synthesis and characterization of novel inorganic silica nanoparticle hybrids. It focuses in large part on their potential applications in the medical field. Silica acts as a useful carrier for a variety of compounds and this thesis silica will demonstrate its use as a carrier for boron or gadolinium. Boron-10 and gadolinium-157 have been suggested for the radiological treatment of tumor cells through the process called neutron capture therapy (NCT). Gadolinium is also commonly used as a Magnetic Resonance Imaging (MRI) contrast agent. Particles that carry it have potential theranostic applications of both imaging and treating tumors. Chapter 1 presents a background on synthetic strategies and usages of silica nanoparticles, and NCT theory. Chapter 2 describes a procedure to create mesoporous metal chelating silica nanoparticles, mDTTA. This is achieved via a co-condensation of tetraethoxysilane (TEOS) and 3-trimethoxysilyl-propyl diethylenetriamine (SiDETA) followed by a post-synthesis modification step with bromoacetic acid (BrAA). These particles have a large surface area and well-defined pores of ~2 nm. The mDTTA nanoparticles were used to chelate the copper(II), cobalt(II) and gadolinium(III). The chelating of gadolinium is the most interesting since it can be used as a MRI contrast agent and a neutron capture therapeutic. The synthetic procedure developed also allows for the attachment of a fluorophore that gives the gadolinium chelating mDTTA nanoparticles a dual imaging modality. Chapter 3 presents the synthetic method used to produce two classes of large surface area organically modified silica (ORMOSIL) nanoparticles. Condensating the organosilane vinyltrimethoxysilane in a micellar solution results in nanoparticles that are either surface rough (raspberry-like) or mesoporous nanoparticles, which prior to this thesis has not been demonstrated in ORMOSIL chemistry. Furthermore, the vinyl functionalities are modified, using

  15. 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).

  16. 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.

  17. Cerium oxide nanoparticles: green synthesis and biological applications

    PubMed Central

    Charbgoo, Fahimeh; Ahmad, Mansor Bin; Darroudi, Majid

    2017-01-01

    CeO2 nanoparticles (NPs) have shown promising approaches as therapeutic agents in biology and medical sciences. The physicochemical properties of CeO2-NPs, such as size, agglomeration status in liquid, and surface charge, play important roles in the ultimate interactions of the NP with target cells. Recently, CeO2-NPs have been synthesized through several bio-directed methods applying natural and organic matrices as stabilizing agents in order to prepare biocompatible CeO2-NPs, thereby solving the challenges regarding safety, and providing the appropriate situation for their effective use in biomedicine. This review discusses the different green strategies for CeO2-NPs synthesis, their advantages and challenges that are to be overcome. In addition, this review focuses on recent progress in the potential application of CeO2-NPs in biological and medical fields. Exploiting biocompatible CeO2-NPs may improve outcomes profoundly with the promise of effective neurodegenerative therapy and multiple applications in nanobiotechnology. PMID:28260887

  18. Cerium oxide nanoparticles: green synthesis and biological applications.

    PubMed

    Charbgoo, Fahimeh; Ahmad, Mansor Bin; Darroudi, Majid

    2017-01-01

    CeO2 nanoparticles (NPs) have shown promising approaches as therapeutic agents in biology and medical sciences. The physicochemical properties of CeO2-NPs, such as size, agglomeration status in liquid, and surface charge, play important roles in the ultimate interactions of the NP with target cells. Recently, CeO2-NPs have been synthesized through several bio-directed methods applying natural and organic matrices as stabilizing agents in order to prepare biocompatible CeO2-NPs, thereby solving the challenges regarding safety, and providing the appropriate situation for their effective use in biomedicine. This review discusses the different green strategies for CeO2-NPs synthesis, their advantages and challenges that are to be overcome. In addition, this review focuses on recent progress in the potential application of CeO2-NPs in biological and medical fields. Exploiting biocompatible CeO2-NPs may improve outcomes profoundly with the promise of effective neurodegenerative therapy and multiple applications in nanobiotechnology.

  19. Enantioselective Michael additions of nitromethane by a catalytic double activation method using chiral lewis Acid and achiral amine catalysts.

    PubMed

    Itoh, Kennosuke; Kanemasa, Shuji

    2002-11-13

    Reactions of nitromethane with 1-(2-alkenoyl)-3,5-dimethylpyrazoles can be effectively catalyzed by R,R-DBFOX/Ph.Ni(ClO4)2.3H2O and achiral amine bases, each in a catalytic loading of 10 mol %, to give 1-(3-substituted 4-nitrobutanoyl)-3,5-dimethylpyrazoles in high chemical yields. Excellent enantioselectivities up to 98% ee have been achieved. The nitro moiety can be easily reduced on Raney nickel at atmospheric pressure, followed by concurrent cyclization, to give enantiomers of 4-substituted 2-pyrrolidinone derivatives after usual workup. This method can be successfully applied to a short step synthesis of (R)-(-)-rolipram.

  20. 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.

  1. 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%.

  2. Catalytic asymmetric assembly of octahydroindolones: divergent synthesis of lycorine-type amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine.

    PubMed

    Sun, Zhongwen; Zhou, Mingtao; Li, Xiang; Meng, Xueling; Peng, Fangzhi; Zhang, Hongbin; Shao, Zhihui

    2014-05-12

    We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition.

  3. 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

  4. 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.

  5. 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

  6. Synthesis of nanostructured materials for biosensor and fuel cell applications

    NASA Astrophysics Data System (ADS)

    Gil, Maria Paula

    Nanotechnology has attracted the attention of many different fields due to the new and exiting possibilities it entails. However, the future of nanotechnology depends on (i) the successful understanding and discovery of material properties at the nanoscale, (ii) efficient manufacture of nanoscale materials, and (iii) most importantly, incorporation of nanomaterials into real world applications and devices. The purpose of this research is to synthesize macroscale materials for applications such as fuel cell membranes or biosensors by assembly or modification at the nanoscale. This research is concentrated in two main projects. The first project focuses on the direct synthesis of a PEEK fuel cell membrane from sulfonated monomers with nanoscale features. S-PEEK membranes were evaluated for possible fuel cell applications by determining the degree of sulfonation, water swelling, proton conductivity, methanol diffusivity and thermal stability. As synthesized S-PEEK membranes exhibit conductivities (25°C) from 0.02--0.07 S/cm, water swelling from 13--54%, ion-exchange capacities (IEC) from 0.7--1.5 mmol/g and methanol diffusion coefficients from 3 x 10-7 --5 x 10-8 cm2/s at 25°C. These diffusion coefficients are much lower than that of NafionRTM (2 x 10-6 cm2/s), making S-PEEK membranes a good alternative to reduce problems associated with high methanol crossover in direct methanol fuel cells. The second project consists of synthesizing (2D) or (3D) nanowire thin film Pt electrodes for applications as glucose sensors. Although platinum nanowires have shown to have unique properties, it is still challenging to fabricate nanowire devices such as sensors. This research reports the fabrication of platinum nanowires into continuous thin film electrodes and the application as biosensors. The electrodes were synthesized by the following steps: (1) construction of a nanostructured mesoporous thin film template by self-assembly of surfactant and silicate species, (2

  7. Supramolecular hydrogels: synthesis, properties and their biomedical applications.

    PubMed

    Dong, Ruijiao; Pang, Yan; Su, Yue; Zhu, Xinyuan

    2015-07-01

    As a novel class of three-dimensional (3D) hydrophilic cross-linked polymers, supramolecular hydrogels not only display unique physicochemical properties (e.g., water-retention ability, drug loading capacity, biodegradability and biocompatibility, biostability) as well as specific functionalities (e.g., optoelectronic properties, bioactivity, self-healing ability, shape memory ability), but also have the capability to undergo reversible gel-sol transition in response to various environmental stimuli inherent to the noncovalent cross-linkages, thereby showing great potential as promising biomaterial scaffolds for diagnosis and therapy. In this Review, we summarized the recent progress in the design and synthesis of supramolecular hydrogels through specific, directional noncovalent interactions, with particular emphasis on the structure-property relationship, as well as their wide-ranging applications in disease diagnosis and therapy including bioimaging, biodetection, therapeutic delivery, and tissue engineering. We believe that these current achievements in supramolecular hydrogels will greatly stimulate new ideas and inspire persistent efforts in this hot topic area in future.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Direct Hydrothermal Synthesis of Carbonaceous Silver Nanocables for Electrocatalytic Applications.

    PubMed

    Chen, Chuyang; Suryanto, Bryan Harry Rahmat; Zhao, Chuan; Jiang, Xuchuan; Yu, Aibing

    2015-08-05

    This study demonstrates a facile but efficient hydrothermal method for the direct synthesis of both carbonaceous silver (Ag@C core-shell) nanocables and carbonaceous nanotubes under mild conditions (<180 °C). The carbonaceous tubes can be formed by removal of the silver cores via an etching process under temperature control (60-140 °C). The structure and composition are characterized using various advanced microscopic and spectroscopic techniques. The pertinent variables such as temperature, reaction time, and surfactants that can affect the formation and growth of the nanocables and nanotubes are investigated and optimized. It is found that cetyltrimethylammonium bromide plays multiple roles in the formation of Ag@C nanocables and carbonaceous nanotubes including: a shape controller for metallic Ag wires and Ag@C cables, a source of Br(-) ions to form insoluble AgBr and then Ag crystals, an etching agent of silver cores to form carbonaceous tubes, and an inducer to refill silver particles into the carbonaceous tubes to form core-shell structures. The formation mechanism of carbonaceous silver nanostructures depending upon temperature is also discussed. Finally, the electrocatalytic performance of the as-prepared Ag@C nanocables is assessed for the oxidation reduction reaction and found to be very active but much less costly than the commonly used platinum catalysts. The findings should be useful for designing and constructing carbonaceous-metal nanostructures with potential applications in conductive materials, catalysts, and biosensors.

  13. Iridium-catalyzed enantioselective hydrogenation of imines in supercritical carbon dioxide

    SciTech Connect

    Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A.

    1999-07-14

    Supercritical carbon dioxide (scCO{sub 2}) was shown to be a reaction medium with unique properties for highly efficient iridium-catalyzed enantioselective hydrogenation of prochiral imines. Cationic iridium(I) complexes with chiral phosphinodihydrooxazoles, modified with perfluoroalkyl groups in the ligand or in the anion, were synthesized and tested in the hydrogenation of N-(1-phenylethylidene)aniline. Both the side chains and the lipophilic anions increased the solubility, but the choice of the anion also had a dramatic effect on the enantioselectivity with tetrakis-3,5-bis(trifluoromethyl)phenylborate (BARF) leading to the highest asymmetric induction. (R)-N-phenyl-1-phenylethylamine was formed quantitatively within 1 h in scCO{sub 2}[d(CO{sub 2}) = 0.75 g mL{sup {minus}1}] at 40 C and a H{sub 2} pressure of 30 bar with enantiomeric excesses of up to 81% using 0.078 mol % catalyst. The use of scCO{sub 2} instead of conventional solvents such as CH{sub 2}Cl{sub 2} allowed the catalyst loading to be lowered significantly owing to a change in the rate profile of the reaction. the homogeneous nature of the catalytically active species under the reaction conditions was demonstrated and was found to depend strongly on the composition of the reaction mixture and especially on the presence of the substrate. Utilizing the selective extractive properties of scCO{sub 2}, the product could be readily separated from the catalyst, which could be recycled several times without significant loss of activity and enantioselectivity. High-pressure FT-IR and NMR investigations revealed that the reactivity of the products to form the corresponding carbamic acids plays an important role for the application of this new methodology.

  14. 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

  15. 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

  16. 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

  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. 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.

  19. 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…

  20. 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

  1. 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

  2. Green Synthesis, Characterization, and Application of Metal-based Nanomaterials

    NASA Astrophysics Data System (ADS)

    Lewis, Crystal Shenandoa

    Metal-based nanomaterials have attracted significant research interest due to their unique size-dependent optical, magnetic, electronic, thermal, mechanical, and chemical properties as compared with their bulk counterparts. These advantageous and tailorable properties render these materials as ideal candidates for catalysis, photovoltaics, and even biomedical applications. However, nanomaterials are typically synthesized via chemical or physical processes, which are continuing to rise in cost, complexity, and toxicity. As a result, 'milder' and more environmentally benign nanoscale synthetic methodologies, particularly U-tube double diffusion, molten salt, and hydrothermal techniques, have been utilized to mitigate for these drawbacks. Moreover, these efficient and facile techniques coupled with the unique attributes of nanomaterials will aid in a more practical translation from the lab scale to industry with potential applications spanning from electronics, energy, to medicine. In this thesis, we will discuss the sustainable synthesis of crystalline elemental copper (Cu), nickel (Ni), magnetic spinel ferrites (MFe2O 4 wherein M is Co, Ni, or Zn), rare earth ion doped-calcium titanate (RE-CaTiO3), and hematite (alpha-Fe2O3) as well as our ability to tailor the size and/or morphology and hence tune their properties for potential applications in solar cells and biomedicine. Specifically, for the Cu and Ni nanowires (NWs), the diameters have been dictated by the various template diameters used in the U-tube double diffusion technique. Subsequently, their photocatalytic properties were observed when coupled with TiO2 NPs. For MFe2O4, RE-CaTiO3, and alpha-Fe2O3 nanostructures, the hydrothermal method was employed wherein various parameters such as reaction temperature, concentration, and addition of surfactant were varied to influence their morphology and/or composition. For example, as the reaction temperature was increased, ultrasmall MFe2O4 particles transformed from

  3. Novel Flame-Based Synthesis of Nanowires for Multifunctional Application

    DTIC Science & Technology

    2015-05-13

    D. Tse, Nasir K. Memon. Flame synthesis of carbon nanotubes and few- layer graphene on metal-oxide spinel powders, Carbon, (11 2013): 478. doi...Jaluria, Y., “Flame Synthesis of Few- Layer Graphene,” ASME International Mechanical Engineering Congress Conference, Nov 11 - 17, 2011, Denver, CO...Dunham, S., Kear, B.H., and Tse, S.D., “Flame Synthesis of Carbon Nanotubes and Few- Layer Graphene on Metal-Oxide Spinel Powders,” Carbon 63:478-486

  4. Substrate Specificity and Enantioselectivity of 4-Hydroxyacetophenone Monooxygenase

    PubMed Central

    Kamerbeek, Nanne M.; Olsthoorn, Arjen J. J.; Fraaije, Marco W.; Janssen, Dick B.

    2003-01-01

    The 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB catalyzes NADPH- and oxygen-dependent Baeyer-Villiger oxidation of 4-hydroxyacetophenone to the corresponding acetate ester. Using the purified enzyme from recombinant Escherichia coli, we found that a broad range of carbonylic compounds that are structurally more or less similar to 4-hydroxyacetophenone are also substrates for this flavin-containing monooxygenase. On the other hand, several carbonyl compounds that are substrates for other Baeyer-Villiger monooxygenases (BVMOs) are not converted by HAPMO. In addition to performing Baeyer-Villiger reactions with aromatic ketones and aldehydes, the enzyme was also able to catalyze sulfoxidation reactions by using aromatic sulfides. Furthermore, several heterocyclic and aliphatic carbonyl compounds were also readily converted by this BVMO. To probe the enantioselectivity of HAPMO, the conversion of bicyclohept-2-en-6-one and two aryl alkyl sulfides was studied. The monooxygenase preferably converted (1R,5S)-bicyclohept-2-en-6-one, with an enantiomeric ratio (E) of 20, thus enabling kinetic resolution to obtain the (1S,5R) enantiomer. Complete conversion of both enantiomers resulted in the accumulation of two regioisomeric lactones with moderate enantiomeric excess (ee) for the two lactones obtained [77% ee for (1S,5R)-2 and 34% ee for (1R,5S)-3]. Using methyl 4-tolyl sulfide and methylphenyl sulfide, we found that HAPMO is efficient and highly selective in the asymmetric formation of the corresponding (S)-sulfoxides (ee > 99%). The biocatalytic properties of HAPMO described here show the potential of this enzyme for biotechnological applications. PMID:12514023

  5. Capillary electrophoretic enantioselective determination of zopiclone and its impurities.

    PubMed

    Tonon, Milena Araújo; Bonato, Pierina Sueli

    2012-06-01

    A capillary electrophoretic enantioselective method with UV detection was developed and validated for the simultaneous quantification of zopiclone enantiomers and its impurities, zopiclone-N-oxide enantiomers, and 2-amino-5-chloropyridine, in tablets. The analytes were extracted from the tablets using ACN and were separated in an uncoated fused-silica capillary (50 μm, 42 cm effective length, 50 cm total length) using 80 mM sodium phosphate buffer pH 2.5 and 5 mM carboxymethyl-β-cyclodextrin as running buffer. The analytes and the internal standard (trimethoprim) were detected at 305 and 200 nm, respectively. A voltage of 27 kV was applied and the capillary temperature was maintained at 25°C. All enantiomers were analyzed within 8 min and linear calibration curves over the concentration range of 0.4-0.8 mg mL⁻¹ for each zopiclone enantiomer, 0.8-1.6 μg mL⁻¹ for 2-amino-5-chloropyridine and 0.4-0.8 μg mL⁻¹ for each zopiclone-N-oxide enantiomer were obtained. The coefficients of correlation obtained for the linear curves were greater than 0.99. The intra-day and inter-day accuracy and precision were lower than 2% for all analytes. This validated method was employed to study the degradation and racemization of zopiclone under stress conditions. This application demonstrated the importance of a stability-indicating assay method for this drug.

  6. PDMS based microfluidic chips and their application in material synthesis

    NASA Astrophysics Data System (ADS)

    Gong, Xiuqing

    Microfluidics is a highly interdisciplinary science which is to deal with the behavior, control and manipulation of fluids that are constrained to sub-milimeter scale. It incorporates the knowledge and technique intersecting physics, chemistry, mechanics, nanoscience and biotechnology, with practical applications to the design of systems in which small volumes of fluids will be used. In this thesis, we started our research from GER fluid synthesis which then is applied to designing different functions of microfluidic devices, valve, pump, and mixer. We built a way to correlate mechanical signal with electric signal by soft matter. The mechanical devices based GER fluid had good operating stability and mechanical performance. We studied how to improve the performance of GER fluid by increasing the yield stress while avoiding the sendimentation of nanoparticles in GER suspension. The meaning of this work is to enhance the stability and mechanical strength of GER fluid when it is applyed to the microfluidc channels. We tried different oils and studied the particle size for the GER effect. The largest yield stress which amounts to 300 kPa is achievable compared to previous GER fluid with 100 kPa. Microfluidic reactor, directing the flow of microliter volumes along microscale channels, offers the advantages of precise control of reagent loading, fast mixing and an enhanced reaction rate, cessation of the reaction at specific stages, and more. Basically, there are two microfluidic flow regimes, continuous flow and segmented flow (suspended droplets, channel-spanning slug, and wall-wetting films). Both flow regimes offer chemical reaction applications, e.g., continuous flow formation of polymer nanospheres and inorganic nanoparticles, size- and shape-control synthesis by segmented flow, and precipitate-forming reactions in droplets, wherein the segmented flow has gained more popularity in that area. The compartmentalization of segmented flow offers advantages to chemical

  7. 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.

  8. Synthesis, Characterization, and Application of Hollow Carbon Nanostructures

    NASA Astrophysics Data System (ADS)

    Song, Yian

    This dissertation describes fundamental studies of hollow carbon nanostructures, which may be used as electrodes for practical energy storage applications such as batteries or supercapacitors. Electron microscopy is heavily utilized for the nanoscale characterization. To control the morphology of hollow carbon nanostructures, ZnO nanowires serve as sacrificial templates. The first part of this dissertation focuses on the optimization of synthesis parameters and the scale-up production of ZnO nanowires by vapor transport method. Uniform ZnO nanowires with 40 nm width can be produced by using 1100 °C reaction temperature and 20 sccm oxygen flow rate, which are the two most important parameters. The use of ethanol as carbon source with or without water steam provides uniform carbonaceous deposition on ZnO nanowire templates. The amount of as-deposited carbonaceous material can be controlled by reaction temperature and reaction time. Due to the catalytic property of ZnO surface, the thicknesses of carbonaceous layers are typically in nanometers. Different methods to remove the ZnO templates are explored, of which hydrogen reduction at temperatures higher than 700 °C is most efficient. The ZnO templates can also be removed under ethanol environment, but the temperatures need to be higher than 850 °C for practical use. Characterizations of hollow carbon nanofibers show that the hollow carbon nanostructures have a high specific surface area (>1100 m2/g) with the presence of mesopores ( 3.5 nm). The initial data on energy storage as electrodes of electrochemical double layer capacitors show that high specific capacitance (> 220 F/g) can be obtained, which is related to the high surface area and unique porous hollow structure with a thin wall.

  9. Organocatalytic enantioselective indole alkylations of alpha,beta-unsaturated ketones.

    PubMed

    Chen, Wei; Du, Wei; Yue, Lei; Li, Rui; Wu, Yong; Ding, Li-Sheng; Chen, Ying-Chun

    2007-03-07

    The C3-selective enantioselective Michael-type Friedel-Crafts alkylations of indoles with nonchelating alpha,beta-unsaturated alkyl ketones, catalysed by a chiral primary amine derived from natural cinchonine, were investigated. The reactions, in the presence of 30 mol% catalyst, were smoothly conducted at 0 to -20 degrees C. Moderate to good ee (47-89%) has been achieved.

  10. Catalytic enantioselective cyclization and C3-fluorination of polyenes.

    PubMed

    Cochrane, Nikki A; Nguyen, Ha; Gagne, Michel R

    2013-01-16

    (Xylyl-phanephos)Pt(2+) in combination with XeF(2) mediates the consecutive diastereoselective cation-olefin cyclization/fluorination of polyene substrates. Isolated yields were typically in the 60-69% range while enantioselectivities reached as high as 87%. The data are consistent with a stereoretentive fluorination of a P(2)Pt-alkyl cation intermediate.

  11. 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

  12. Anisotropic nanomaterials: Synthesis, optical and magnetic properties, and applications

    NASA Astrophysics Data System (ADS)

    Banholzer, Matthew John

    As nanoscience and nanotechnology mature, anisotropic metal nanostructures are emerging in a variety of contexts as valuable class of nanostructures due to their distinctive attributes. With unique properties ranging from optical to magnetic and beyond, these structures are useful in many new applications. Chapter two discusses the nanodisk code: a linear array of metal disk pairs that serve as surface-enhanced Raman scattering substrates. These multiplexing structures employ a binary encoding scheme, perform better than previous nanowires designs (in the context of SERS) and are useful for both convert encoding and tagging of substrates (based both on spatial disk position and spectroscopic response) as well as biomolecule detection (e.g. DNA). Chapter three describes the development of improved, silver-based nanodisk code structures. Work was undertaken to generate structures with high yield and reproducibility and to reoptimize the geometry of each disk pair for maximum Raman enhancement. The improved silver structures exhibit greater enhancement than Au structures (leading to lower DNA detection limits), convey additional flexibility, and enable trinary encoding schemes where far more unique structures can be created. Chapter four considers the effect of roughness on the plasmonic properties of nanorod structures and introduces a novel method to smooth the end-surfaces of nanorods structures. The smoothing technique is based upon a two-step process relying upon diffusion control during nanowires growth and selective oxidation after each step of synthesis is complete. Empirical and theoretical work show that smoothed nanostructures have superior and controllable optical properties. Chapter five concerns silica-encapsulated gold nanoprisms. This encapsulation allows these highly sensitive prisms to remain stable and protected in solution, enabling their use as class-leading sensors. Theoretical study complements the empirical work, exploring the effect of

  13. Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.

    PubMed

    Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas

    2006-01-01

    The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

  14. Recent progress on the synthesis and applications of carbon based nanostructures.

    PubMed

    Rajavel, K; Minitha, C R; Ranjith, K S; Rajendra Kumar, R T

    2012-06-01

    This article reviews the latest developments in the synthesis of Graphene, Carbon nanotubes and graphene/CNT based devices based on patents, patent applications and articles published in the last two years. A brief introduction about CNT and Graphene is presented, followed by the latest techniques and advanced processing for the large scale synthesis of Graphene and CNTs. Furthermore, a brief account of emerging devices based on applications of CNTs and graphene not limited to sensors, high speed electronics, energy harvesting and storage applications are presented.

  15. Phytotoxicity of chiral herbicide bromacil: Enantioselectivity of photosynthesis in Arabidopsis thaliana.

    PubMed

    Chen, Zunwei; Zou, Yuqin; Wang, Jia; Li, Meichao; Wen, Yuezhong

    2016-04-01

    With the wide application of chiral herbicides and the frequent detection of photosystem II (PSII) herbicides, it is of great importance to assess the direct effects of PSII herbicides on photosynthesis in an enantiomeric level. In the present study, the enantioselective phytotoxicity of bromacil (BRO), typical photosynthesis inhibition herbicide, on Arabidopsis thaliana was investigated. The results showed that S-BRO exhibited a greater inhibition of electron transmission in photosystem I (PSI) of A. thaliana than R-BRO by inhibiting the transcription of fnr 1. S-BRO also changed the chlorophyll fluorescence parameters Y (II), Y (NO), and Y (NPQ) to a greater extent than R-Bro. Transcription of genes psbO2, Lhcb3 and Lhcb6 was down-regulated in an enantioselective rhythm and S-BRO caused more serious influence, indicating that S-BRO did worse damage to the photosystem II (PSII) of A. thaliana than R-BRO. This study suggested that S-BRO disturbed the photosynthesis of plants to a larger extent than R-BRO and provided a new sight to evaluate the phytotoxicity of chiral herbicides.

  16. Enantioselective stable isotope analysis (ESIA) of polar Herbicides

    NASA Astrophysics Data System (ADS)

    Maier, Michael; Qiu, Shiran; Elsner, Martin

    2013-04-01

    The complexity of aquatic systems makes it challenging to assess the environmental fate of chiral micropolutants. As an example, chiral herbicides are frequently detected in the environment (Buser and Muller, 1998); however, hydrological data is needed to determine their degradability from concentration measurements. Otherwise declining concentrations cannot unequivocally be attributed to degradation, but could also be caused by dilution effects. In contrast, isotope ratios or enantiomeric ratios are elegant alternatives that are independent of dilution and can even deliver insights into reaction mechanisms. To combine the advantages of both approaches we developed an enatioselective stable isotope analysis (ESIA) method to investigate the fate of the chiral herbicides 4-CPP ((RS)-2-(4-chlorophenoxy)-propionic acid), mecoprop (2-(4-Chloro-2-methylphenoxy)-propionic acid) and dichlorprop (2-(2,4-Dichlorophenoxy)-propionic acid). After testing the applicable concentration range of the method, enantioselective isotope fractionation was investigated by microbial degradation using dichlorprop as a model compound. The method uses enantioselective gas-chromatography (GC) to separate enantiomers. Subsequently samples are combusted online to CO2 and carbon isotope ratios are determined for each enantiomer by isotope-ratio-mass-spectrometry (IRMS). Because the analytes contain a polar carboxyl-group, samples were derivatised prior to GC-IRMS analysis with methanolic BF3 solution. Precise carbon isotope analysis (2σ ≤0.5‰) was achieved with a high sensitivity of ≥ 7 ng C that is needed on column for one analysis. Microbial degradation of the model compound dichlorprop was conducted with Delftia acidovorans MC1 and pronounced enantiomer fractionation, but no isotope fractionation was detected. The absence of isotope fractionation can be explained by two scenarios: either the degrading enzyme has no isotopic preference, or another step in the reaction without an isotopic

  17. Synthesis and characterization of iron based nanoparticles for novel applications

    NASA Astrophysics Data System (ADS)

    Khurshid, Hafsa

    The work in this thesis has been focused on the fabrication and characterization of iron based nanoparticles with controlled size and morphology with the aim: (i) to investigate their properties for potential applications in MICR toners and biomedical field and (ii) to study finite size effects on the magnetic properties of the nanoparticles. For the biomedical applications, core/shell structured iron/iron-oxide and hollow shell nanoparticles were synthesized by thermal decomposition of iron organometallic compounds [Fe(CO)5] at high temperature. Core/shell structured iron/iron-oxide nanoparticles have been prepared in the presence of oleic acid and oleylamine. Particle size and composition was controlled by varying the reaction parameters during synthesis. The as-made particles are hydrophobic and not dispersible in water. Water dispersibility was achieved by ligand exchange a with double hydrophilic diblock copolymer. Relaxometery measurements of the transverse relaxation time T2 of the nanoparticles solution at 3 Tesla confirm that the core/shell nanoparticles are an excellent MRI contrast agent using T2 weighted imaging sequences. In comparison to conventionally used iron oxide nanoparticles, iron/iron-oxide core/shell nanoparticles offer four times stronger T2 shortening effect at comparable core size due to their higher magnetization. The magnetic properties were studied as a function of particle size, composition and morphology. Hollow nanostructures are composed of randomly oriented grains arranged together to make a shell layer and make an interesting class of materials. The hollow morphology can be used as an extra degree of freedom to control the magnetic properties. Owing to their hollow morphology, they can be used for the targeted drug delivery applications by filling the drug inside their cavity. For the magnetic toners applications, particles were synthesized by chemically reducing iron salt using sodium borohydride and then coated with polyethylene

  18. Biogenic synthesis of metal nanoparticles from actinomycetes: biomedical applications and cytotoxicity.

    PubMed

    Golinska, Patrycja; Wypij, Magdalena; Ingle, Avinash P; Gupta, Indarchand; Dahm, Hanna; Rai, Mahendra

    2014-10-01

    Biogenic synthesis of metal nanoparticles has been well proved by using bacteria, fungi, algae, actinomycetes, plants, etc. Among the different microorganisms used for the synthesis of metal nanoparticles, actinomycetes are less known. Although, there are reports, which have shown that actinomycetes are efficient candidates for the production of metal nanoparticles both intracellularly and extracellularly. The nanoparticles synthesized by the members of actinomycetes present good polydispersity and stability and possess significant biocidal activities against various pathogens. The present review focuses on biological synthesis of metal nanoparticles and their application in medicine. In addition, the toxicity of these biogenic metal nanoparticles to human beings and environment has also been discussed.

  19. 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

  20. Synthesis, toxicity, biocompatibility, and biomedical applications of graphene and graphene-related materials.

    PubMed

    Gurunathan, Sangiliyandi; Kim, Jin-Hoi

    2016-01-01

    Graphene is a two-dimensional atomic crystal, and since its development it has been applied in many novel ways in both research and industry. Graphene possesses unique properties, and it has been used in many applications including sensors, batteries, fuel cells, supercapacitors, transistors, components of high-strength machinery, and display screens in mobile devices. In the past decade, the biomedical applications of graphene have attracted much interest. Graphene has been reported to have antibacterial, antiplatelet, and anticancer activities. Several salient features of graphene make it a potential candidate for biological and biomedical applications. The synthesis, toxicity, biocompatibility, and biomedical applications of graphene are fundamental issues that require thorough investigation in any kind of applications related to human welfare. Therefore, this review addresses the various methods available for the synthesis of graphene, with special reference to biological synthesis, and highlights the biological applications of graphene with a focus on cancer therapy, drug delivery, bio-imaging, and tissue engineering, together with a brief discussion of the challenges and future perspectives of graphene. We hope to provide a comprehensive review of the latest progress in research on graphene, from synthesis to applications.