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Sample records for efficient stereoselective synthesis

  1. Efficient asymmetric synthesis of novel gastrin receptor antagonist AG-041R via highly stereoselective alkylation of oxindole enolates.

    PubMed

    Emura, Takashi; Esaki, Toru; Tachibana, Kazutaka; Shimizu, Makoto

    2006-10-27

    An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.

  2. Total stereoselective synthesis of (+)-goniothalesdiol.

    PubMed

    Carreño, M Carmen; Hernández-Torres, Gloria; Urbano, Antonio; Colobert, Françoise

    2005-11-24

    [reaction: see text] The stereoselective synthesis of (+)-goniothalesdiol (1) was accomplished in nine steps starting from commercially available (-)-(2S,3S)-dimethyl D-tartrate (3). The key features were a completely diastereoselective reduction of a beta-ketosulfoxide to generate the stereogenic center at C-5 in 7 and formation of the 2,5-cis-substituted tetrahydrofuran ring in 10 from a stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization/deoxygenation.

  3. Stereoselective Synthesis of Tilivalline(1).

    PubMed

    Nagasaka, Tatsuo; Koseki, Yuji

    1998-10-02

    Tilivalline 1, a metabolite from Klebsiella pneumoniae var. ocytoca, was easily synthesized in five steps from (S)-proline and 3-(benzyloxy)isatoic anhydride 4g. This synthesis is based on modified Curtius reactions of 3-substituted phthalic anhydrides 11 to 3-substituted isatoic anhydrides 4, conversion of lactams 6 to the acyliminium precursors 7 and stereoselective introduction of indole from the less hindered side of 7.

  4. 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.

  5. Organoselenium-catalyzed, hydroxy-controlled regio- and stereoselective amination of terminal alkenes: efficient synthesis of 3-amino allylic alcohols.

    PubMed

    Deng, Zhimin; Wei, Jialiang; Liao, Lihao; Huang, Haiyan; Zhao, Xiaodan

    2015-04-17

    An efficient route to prepare 3-amino allylic alcohols in excellent regio- and stereoselectivity in the presence of bases by orangoselenium catalysis has been developed. In the absence of bases α,β-unsaturated aldehydes were formed in up to 97% yield. Control experiments reveal that the hydroxy group is crucial for the direct amination.

  6. Stereoselective Halogenation in Natural Product Synthesis.

    PubMed

    Chung, Won-jin; Vanderwal, Christopher D

    2016-03-24

    At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp(3) -hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.

  7. Witting Reaction Using a Stabilized Phosphorus Ylid: An Efficient and Stereoselective Synthesis of Ethyl Trans-Cinnamate

    ERIC Educational Resources Information Center

    Speed, Traci J.; Mclntyre, Jean P.; Thamattoor, Dasan M.

    2004-01-01

    An instructive experiment for the synthesis of ethyl trans-cinnamate, a pleasant smelling ester used in perfumery and flavoring by the reaction of benzaldehyde with the stable ylid triphenylphosphorane is described. The synthesis, workup and characterization of trans-cinnamate may be accomplished in a single laboratory session with commonly…

  8. Stereoselective synthesis of indolines via organocatalytic thioester enolate addition reactions.

    PubMed

    Kolarovic, Andrej; Käslin, Alexander; Wennemers, Helma

    2014-08-15

    A straightforward stereoselective synthesis route to indolin-3-yl acetates has been developed using organocatalytic addition reactions of monothiomalonates to ortho-bromo nitrostyrenes as the key step. The addition products of this highly stereoselective one-pot addition-deprotection-decarboxylation sequence were easily further converted to the target indolin-3-yl acetates, via an intramolecular Buchwald-Hartwig coupling reaction. The route provided indolin-3-yl acetates bearing tertiary and exocyclic quarternary stereogenic centers in excellent stereoselectivities and overall yields of 34-83%.

  9. Stereoselective synthesis of enantiomerically pure nupharamine alkaloids from castoreum.

    PubMed

    Stoye, Alexander; Quandt, Gabriele; Brunnhöfer, Björn; Kapatsina, Elissavet; Baron, Julia; Fischer, André; Weymann, Markus; Kunz, Horst

    2009-01-01

    An animalic note: The first total synthesis of the all-cis nupharamine 2, an alkaloid from beaver castoreum, is based on the stereoselective domino Mannich-Michael reaction of N-galactosylfurylaldimine to give 1 (Piv = pivaloyl), subsequent conjugate cuprate addition, and stereoselective protonation of the enolate. These reactions are all controlled by the carbohydrate. Protonation of the enolate after cleavage of the auxiliary leads to epimer 3.

  10. Stereoselective synthesis of nicotinamide beta-riboside and nucleoside analogs.

    PubMed

    Franchetti, Palmarisa; Pasqualini, Michela; Petrelli, Riccardo; Ricciutelli, Massimo; Vita, Patrizia; Cappellacci, Loredana

    2004-09-20

    The beta-anomers of N-ribofuranosylnicotine-3-carboxamide (beta-NAR) and its nicotinic acid analog (beta-NaR) were obtained by stereoselective synthesis via glycosylation of the presilylated bases under Vorbruggen's protocol. A NAR analog, methylated in position 3 of the ribosylic moiety, is also reported.

  11. Synthesis of (+)-Discodermolide by Catalytic Stereoselective Borylation Reactions**

    PubMed Central

    Yu, Zhiyong; Ely, Robert J.

    2014-01-01

    The marine natural product (+)-discodermolide was first isolated in 1990 and, to this day, remains a compelling synthesis target. Not only does the compound possess fascinating biological activity, but it also presents an opportunity to test current methods for chemical synthesis and provides a forum for the inspiration of new reaction development. In this manuscript, we present a synthesis of discodermolide that employs a previously undisclosed stereoselective catalytic diene hydroboration and also establishes a strategy for chiral enolate alkylation. In addition, this synthesis of discodermolide provides the first examples of diene 1,4-diboration and borylative diene-aldehyde couplings in complex molecule synthesis. PMID:25045037

  12. Stereoselective synthesis of pentacyclic steroids functionalized at C-11.

    PubMed

    Ibrahim-Ouali, Malika; Romero, Eugénie; Hamze, Khalil

    2012-09-01

    We set out to describe an efficient and versatile method for preparing pentacyclic steroids diversely substituted at C-11 from cholic acid, via a stereoselective epoxidation and the epoxide opening as the key steps. The characteristic (1)H and (13)C NMR spectroscopic features of the synthesized compounds are reported.

  13. Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ0)

    PubMed Central

    2014-01-01

    Summary A convergent and stereoselective synthesis of chiral cyclopentyl- and cyclohexylamine derivatives of nucleoside Q precursor (PreQ0) has been accomplished. This synthetic route allows for an efficient preparation of 4-substituted analogues with interesting three-dimensional character, including chiral cyclopentane-1,2-diol and -1,2,3-triol derivatives. This unusual substitution pattern provides a useful starting point for the discovery of novel bioactive molecules. PMID:24991286

  14. Stereoselective Synthesis of Quaternary Proline Analogues

    PubMed Central

    Calaza, M. Isabel

    2009-01-01

    This review describes available methods for the diastereoselective and asymmetric synthesis of quaternary prolines. The focus is on the preparation of α-functionalized prolines with the pyrrolidine moiety not embedded in a polycyclic frame. The diverse synthetic approaches are classified according to the bond which is formed to complete the quaternary skeleton. PMID:19655047

  15. Stereoselective Synthesis of β-manno-Glycosides

    NASA Astrophysics Data System (ADS)

    Ishiwata, Akihiro; Ito, Yukishige

    Among the various types of O-glycosides with biological relevance, the β-glycoside of D-mannose (β-manno-glycoside) has been considered as one of the most challenging targets from a synthetic point of view. The majority of synthetic approaches to β-manno-glycoside can be put into two categories (the direct glycosylation and the glycosylation-inversion approaches). Additionally, a variety of intriguing approaches have been investigated with substantial success (alkylative glycosylation of 1,2-stannylene acetal, reductive manipulation of orthoester, intramolecular aglycon delivery, and enzymatic glycosylation). In this chapter, progress in the conceptually demanding β-mannosylation technology will be discussed, including current state of the art, with particular focus upon applications related to the synthesis of glycoprotein-related oligosaccharides.

  16. Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme.

    PubMed

    de la Fuente, Alex; Rísquez-Cuadro, Rocío; Verdaguer, Xavier; García Fernández, José M; Nanba, Eiji; Higaki, Katsumi; Ortiz Mellet, Carmen; Riera, Antoni

    2016-10-04

    Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta β-N-acetylglucosaminidase (β-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards β-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase.

  17. Iminium Ion Cascade Reactions: Stereoselective Synthesis of Quinolizidines and Indolizidines

    PubMed Central

    Amorde, Shawn M.; Jewett, Ivan T.; Martin, Stephen F.

    2009-01-01

    A novel iminium ion cascade reaction has been developed that allows for the stereoselective synthesis of a variety of substituted aza-fused bicycles. The combination of amino allylsilanes and aldehydes (or ketones) was used to synthesize a number of quinolizidines and indolizidines in an one-pot reaction sequence. This technology has been used to effect the facile syntheses of several indolizidine and quinolizidine natural products including, (±)-epilupinine, (±)-tashiromine, and (−)-epimyrtine. Substrate scope has been examined varying the type of amino allylsilanes (primary, secondary and conjugated) and carbonyl compounds (aldehydes and ketones) to give a variety of fused ring structures. Varying the components chosen allows for the inclusion of synthetically useful functional groups at different positions on the core structure. The methodology has been used to construct the tricyclic core structures present in the cylindricine family and halichlorine. PMID:20890382

  18. Experimental and theoretical investigations of the stereoselective synthesis of p-stereogenic phosphine oxides.

    PubMed

    Copey, Laurent; Jean-Gérard, Ludivine; Framery, Eric; Pilet, Guillaume; Robert, Vincent; Andrioletti, Bruno

    2015-06-15

    An efficient enantioselective strategy for the synthesis of variously substituted phosphine oxides has been developed, incorporating the use of (1S,2S)-2-aminocyclohexanol as the chiral auxiliary. The method relies on three key steps: 1) Highly diastereoselective formation of P(V) oxazaphospholidine, rationalized by a theoretical study; 2) highly diastereoselective ring-opening of the oxazaphospholidine oxide with organometallic reagents that takes place with inversion of configuration at the P atom; 3) enantioselective synthesis of phosphine oxides by cleavage of the remaining P-O bond. Interestingly, the use of a P(III) phosphine precursor afforded a P-epimer oxazaphospholidine. Hence, the two enantiomeric phosphine oxides can be synthesized starting from either a P(V) or a P(III) phosphine precursor, which constitutes a clear advantage for the stereoselective synthesis of sterically hindered phosphine oxides.

  19. Stereoselective synthesis of UDP-2-(2-ketopropyl)galactose aided by di-tert-butylsilylene protecting group.

    PubMed

    Sakamoto, Yasuharu; Ohta, Tsuyoshi; Ito, Yukishige

    2015-10-01

    UDP-2-(2-ketopropyl)galactose (1) has been utilized as a valuable probe for profiling proteins modified by O-GlcNAc. In this work, we developed a protocol for efficient synthesis of 1. Thus, 2-methallylgalactose derivative 11, a synthetic intermediate for the compound 1, was prepared by stereoselective iodination and methallylation at C-2 position, through exploitation of 4,6-O-di-tert-butylsilylene protecting group.

  20. Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

    PubMed Central

    Rigamonti, Marco Giulio

    2015-01-01

    Summary The first stereoselective synthesis of lippidulcines A, B and C has been accomplished starting from (+)-hernandulcin, which has been prepared on a multigram scale. The previously assigned absolute configurations have been confirmed. The key steps of this synthesis are based on a modified version of the Kornblum–DeLaMare rearrangement, and on a highly regioselective and stereoselective ketone reduction with the MeCBS reagent. The taste evaluations indicate that none of these sesquiterpenes are sweet, instead the lippidulcine A is a cooling agent with a mint after taste. PMID:26664632

  1. Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters.

    PubMed

    Engl, Oliver D; Fritz, Sven P; Wennemers, Helma

    2015-07-06

    Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin-derived N-Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto's catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin-B receptor antagonist AG-041R.

  2. Recent Progress on the Stereoselective Synthesis of Cyclic Quaternary α-Amino Acids

    PubMed Central

    Cativiela, Carlos; Ordóñez, Mario

    2010-01-01

    The most recent papers describing the stereoselective synthesis of cyclic quaternary α-amino acids are collected in this review. The diverse synthetic approaches are classified according to the size of the ring and taking into account the bond that is formed to complete the quaternary skeleton. PMID:20300486

  3. An Overview of Stereoselective Synthesis of α-Aminophosphonic Acids and Derivatives

    PubMed Central

    Ordóñez, Mario; Rojas-Cabrera, Haydée; Cativiela, Carlos

    2009-01-01

    An overview of all methodologies published during the last few years focused to the stereoselective (diastereoselective or enantioselective) synthesis of α-aminophosphonic acids and derivatives is reported. The procedures have been classified according a retrosynthetic strategy and taking into account the formation of each one of the bonds connected to the chiral centre. PMID:20871799

  4. [Development of highly stereoselective reactions utilizing heteroatoms--asymmetric synthesis of alpha-substituted serines].

    PubMed

    Sano, S

    2000-01-01

    This article reviews the efficient methods for diastereoselective and enantioselective syntheses of alpha-substituted serines. A newly designed bislactim ether, ethyl (5S)- or (5R)-3,6-diethoxy-2,5-dihydro-5-isopropyl-2-pyrazinecarboxylate, was treated with base or Lewis acid-tertiary amine to generate an enolate or enaminate (imine anion, metalloenamine). Alkylation or aldol-type reaction with the resultant enolate or enaminate proceeded in a highly diastereoselective manner to give the corresponding alkylated or aldol products, respectively. Reduction of these products with diisobutylaluminum hydride (DIBAL) followed by hydrolysis with hydrochloric acid afforded the desirable alpha-substituted serines. The enantioselective aldol-type reaction of an achiral bislactim ether, ethyl 3,6-diethoxy-2,5-dihydro-2-pyrazinecarboxylate, was also investigated by employing Sn(OSO2CF3)2-triethylamine in the presence of an external chiral ligand, (--)-sparteine. Not only a stoichiometric amount, but also a catalytic amount of (--)-sparteine promoted the highly enantioselective aldol-type reactions. Interestingly, the stereoselective outcome of the Sn(II)-mediated reaction differed from that of the Mg(II)-mediated one in the aldol-type reaction of the bislactim ethers with aliphatic aldehydes. On the other hand, chemoenzymatic synthesis of enantiomerically pure alpha-substituted serines must also be a convenient and useful procedure. Porcine liver esterase (PLE) or rabbit liver esterase (RLE) catalyzed hydrolysis of the pro-S ester group of diethyl alpha-alkyl-alpha-(benzyloxycarbonylamino)malonates to afford (R)-ethyl alpha-alkyl-alpha-(benzyloxycarbonylamino)malonates each in excellent enantiomeric excess. Enantiodivergent reductions of these acid esters readily proceeded to furnish both the corresponding enantiomeric alpha-substituted serines. Finally, the application of these methodologies mentioned above to a total synthesis of ISP-I (a potent immunosuppressive principle in

  5. Stereoselective synthesis of heterocyclic cage compounds by domino conjugate additions.

    PubMed

    Carreño, M Carmen; Luzón, Carmen García; Ribagorda, María

    2002-01-04

    Heterocyclic cage compounds have been stereoselectively synthesized from enantiopure [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols or their amine analogues and 2-(trimethylsilyloxy)furan in the presence of Bu4NF. The method is particularly valuable not only because of the stereochemical control but also because the reactions occur in an experimentally simple one-pot procedure through a domino sequence of three consecutive conjugate additions. The intermediate 1,4-adducts could be isolated when the reaction was carried out in the presence of BF3 x OEt2.

  6. Stereoselective synthesis of 2,5-disubstituted morpholines using a palladium-catalyzed hydroamination reaction.

    PubMed

    McGhee, Alicia; Cochran, Brian M; Stenmark, Torrey A; Michael, Forrest E

    2013-08-04

    A palladium-catalyzed hydroamination reaction is the key step in a stereoselective synthesis of 2,5-disubstituted and 2,3,5-trisubsituted morpholines from carbamate-protected aziridines. Aziridines are selectively attacked at the more substituted position by unsaturated alcohol nucleophiles using Lewis acid catalysts. Palladium-catalyzed hydroamination of the resulting aminoalkenes gives morpholines as a single diastereomer in excellent yield.

  7. Highly Efficient and Stereoselective Construction of Bispirooxindole Derivatives via a Three-Component 1,3-Dipolar Cycloaddition Reaction.

    PubMed

    Xu, Qin; Wang, De; Wei, Yin; Shi, Min

    2014-06-01

    A highly regio- and stereoselective synthesis of bispirooxindoles by 1,3-dipolar cycloaddition of in situ generated azomethine ylides from isatin and proline to different electron-deficient alkenes has been developed. The synthesis affords the desired bispiro scaffold compounds in excellent yields with high regioselectivity under mild conditions. The stereochemistry was determined by single-crystal X-ray analysis.

  8. Cooperative Brønsted Acid-Type Organocatalysis for the Stereoselective Synthesis of Deoxyglycosides

    PubMed Central

    2016-01-01

    A practical approach for the α-stereoselective synthesis of deoxyglycosides using cooperative Brønsted acid-type organocatalysis has been developed. The method is tolerant of a wide range of glycoside donors and acceptors, and its versatility is exemplified in the one-pot synthesis of a trisaccharide. Mechanistic studies suggest that thiourea-induced acid amplification of the chiral acid via H-bonding is key for the enhancement in reaction rate and yield, while stereocontrol is dependent on the chirality of the acid. PMID:28004941

  9. Reactions between Grignard reagents and heterocyclic N-oxides: stereoselective synthesis of substituted pyridines, piperidines, and piperazines.

    PubMed

    Andersson, Hans; Olsson, Roger; Almqvist, Fredrik

    2011-01-21

    In this perspective we discuss the recent developments of stereoselective synthesis of substituted pyridines, piperidines, and piperazines from cheap and commercially readily available starting materials. Pyridine N-oxides and pyrazine N-oxides are reacted with alkyl, aryl, alkynyl and vinyl Grignard reagents to give a diverse set of heterocycles in high yields. Optically active substituted piperazines are obtained by an asymmetric reaction from pyrazine N-oxides using sparteine as chiral ligand. In addition, a stereoselective synthesis of dienal-oximes from the reaction between pyridine N-oxides and Grignard reagents is presented, which results in a useful intermediate for the synthesis of a diverse set of compounds.

  10. Highly Stereoselective Total Synthesis of Fully Hydroxy-Protected Mycolactones A and B and Their Stereoisomerization upon Deprotection

    PubMed Central

    Wang, Guangwei; Yin, Ning

    2013-01-01

    Unprecedentedly efficient and highly (≥98%) stereoselective syntheses of mycolactones A and B sidechains relied heavily on Pd-catalyzed alkenylation (Negishi version) and were completed in 11 longest linear steps from ethyl (S)-3-hydroxybutyrate in 12% and 11% overall yields, respectively, roughly corresponding to an average of 82% yield per step. The synthesis of mycolactone core was realized by using Pd-catalyzed alkenyl–allyl coupling and an epoxide-opening reaction with a trialkylalkenylaluminate as key steps. Fully hydroxy-protected mycolactones A and B of ≥98% isomerical purity were synthesized successfully for the first time. However, unexpected 4/3-5/4 inseparable mixtures of mycolactones A and B were obtained upon deprotection. PMID:21412860

  11. Exploitation of a Multienzymatic Stereoselective Cascade Process in the Synthesis of 2-Methyl-3-Substituted Tetrahydrofuran Precursors.

    PubMed

    Brenna, Elisabetta; Crotti, Michele; Gatti, Francesco G; Marinoni, Ludovico; Monti, Daniela; Quaiato, Sara

    2017-02-17

    Enantiopure 2-methyl-3-substituted tetrahydrofurans are key precursors of several biologically active products (drugs, flavors, and agrochemicals). Thus, a stereocontrolled and efficient methodology for the obtainment of these synthons is highly desirable. We exploited a two-step multienzymatic stereoselective cascade reduction of α-bromo-α,β-unsaturated ketones to give the corresponding bromohydrins in good yields, with high ee and de values. The cascade process is catalyzed by an ene-reductase and an alcohol dehydrogenase. Further manipulations of these bromohydrins, by two diastereodivergent routes, allowed the preparation of the tetrahydrofuran synthons. One route is based on a lipase catalyzed cleavage of the protecting group. The second route is characterized by a camphor sulfonic acid mediated isomerization of a β-hydroxyepoxide to give the tetrahydrofuran-2-ol. Finally, the synthesis of the most odorous and pleasant stereoisomer of the roasted meat aroma, i.e., (2S,3R)-2-methyl-3-thioacetate tetrahydrofuran, is reported as well.

  12. Stereoselective synthesis of protectin D1: A potent anti-inflammatory and proresolving lipid mediator

    PubMed Central

    Aursnes, M.; Tungen, J. E.; Vik, A.; Dalli, J.; Hansen, T. V.

    2014-01-01

    A convergent stereoselective synthesis of the potent anti-inflammatory, proresolving and neuroprotective lipid mediator protectin D1 (2) has been achieved in 15% yield over eight steps. The key features were a stereocontrolled Evans-aldol reaction with Nagao’s chiral auxiliary and a highly selective Lindlar reduction of internal alkyne 23, allowing the sensitive conjugated E,E,Z-triene to be introduced late in the preparation of 2. The UV and LC/MS-MS data of synthetic protectin D1 (2) matched those obtained from endogenously produced material PMID:24253202

  13. Total synthesis of fostriecin: via a regio- and stereoselective polyene hydration, oxidation, and hydroboration sequence.

    PubMed

    Gao, Dong; O'Doherty, George A

    2010-09-03

    A total synthesis of the fostriecin has been achieved in 24 steps from enyne 11. The lactone moiety was installed by a Leighton allylation and Grubbs ring-closing metathesis reaction. The highly reactive Z,Z,E-triene moiety was installed via a late-stage Suzuki-Miyaura cross-coupling of a remarkably stable Z-vinyl boronate. The relative and absolute stereocenters of the C-8,9,11 triol were generated with a regio- and stereoselective asymmetric hydration/oxidation sequence.

  14. Stereoselective synthesis of stable-isotope-labeled amino acids

    SciTech Connect

    Unkefer, C.J.; Martinez, R.A.; Silks, L.A. III; Lodwig, S.N.

    1994-12-01

    For magnetic resonance and vibrational spectroscopies to reach their full potential, they must be used in combination with sophisticated site-specific stable isotope labeling of biological macromolecules. Labeled amino acids are required for the study of the structure and function of enzymes and proteins. Because there are 20 common amino acids, each with its own distinguishing chemistry, they remain a synthetic challenge. The Oppolzer chiral auxiliary provides a general tool with which to approach the synthesis of labeled amino acids. By using the Oppolzer auxiliary, amino acids can be constructed from several small molecules, which is ideal for stable isotope labeling. In addition to directing the stereochemistry at the {alpha}-carbon, the camphorsultam can be used for stereo-specific isotope labeling at prochiral centers in amino acids. By using the camphorsultam auxiliary we have the potential to synthesize virtually any isotopomer of all of the common amino acids.

  15. Stereoselective Alkylation of the Vinylketene Silyl N,O-Acetal and Its Application to the Synthesis of Mycocerosic Acid.

    PubMed

    Nakamura, Tatsuya; Kubota, Kei; Ieki, Takanori; Hosokawa, Seijiro

    2016-01-04

    Stereoselective alkylation of the vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using activated alkyl halides including allyl iodides, benzyl iodides, and propargyl iodide with Ag(I) ion in the presence of BF3·OEt2. The reaction proceeded to give reduced polyketides in high stereoselectivity. The synthesis of mycocerosic acid, a component of the cell envelope of Mycobacterium tuberculosis, has been accomplished by this methodology. During the synthetic studies, 2-methylbenzimidazole was found to be a bulky proton source which worked in the presence of liquid ammonia.

  16. Stereoselective synthesis of (all-Z)-hentriaconta-3,6,9,12,15,19,22,25,28-nonaene.

    PubMed

    Filippova, Liudmila; Aarum, Ida; Ringdal, Martine; Dahl, Martin Kirkhus; Hansen, Trond Vidar; Stenstrøm, Yngve

    2015-04-28

    Several microorganisms produce small quantities of polyunsaturated hydrocarbons and such natural products are of interest. Starting from the ethyl ester of eicosapentaenoic acid, the total synthesis of the natural product (all-Z)-hentriaconta-3,6,9,12,15,19,22,25,28-nonaene has been achieved in eight steps and 15% overall yield. The synthesis is based on a stereoselective Wittig reaction and confirms the all-Z-configuration of the nine double bonds in this highly unsaturated natural product.

  17. A new method for the stereoselective synthesis of alpha- and beta-glycosylamines using the Burgess reagent.

    PubMed

    Nicolaou, K C; Snyder, Scott A; Nalbandian, Annie Z; Longbottom, Deborah A

    2004-05-26

    Although glycosylamines constitute an important group of carbohydrates from the standpoint of biology and medicine, methods for their synthesis typically lack substrate generality and/or result in variable stereoselectivity, especially in complex contexts. In this communication, we report an operationally simple method for the synthesis of both alpha- and beta-glycosylamines using the Burgess reagent that overcomes many of these limitations in a bare minimum of synthetic steps.

  18. A Maitland-Japp inspired synthesis of dihydropyran-4-ones and their stereoselective conversion to functionalised tetrahydropyran-4-ones.

    PubMed

    Clarke, Paul A; Sellars, Philip B; Nasir, Nadiah Mad

    2015-04-28

    The Maitland-Japp reaction has been extended to the synthesis of highly functionalised dihydropyran-4-ones. These dihydropyran-4-ones can in turn be converted stereoselectively into tetrahydropyran-4-ones with tertiary and quaternary stereocentres via the one-pot addition of hydride or carbon nucleophiles and trapping with carbon electrophiles. The utility of this method is demonstrated by providing access to the functionalised tetrahydropyran units present in a component of the Civet fragrance and the anticancer polyketide lasonolide A.

  19. Stereoselective Construction of all-anti Polypropionate Modules: Synthesis of the C5-C10 Fragment of Streptovaricin U

    PubMed Central

    Torres, Wildeliz; Rodríguez, Raúl R.; Prieto, José A.

    2009-01-01

    A concise non-aldol approach for the stereoselective construction of all-anti polypropionate fragments was developed. The iterative epoxide-based methodology consists of the syn-selective epoxidation of cis homoallylic alcohols using the VO(acac)2 catalyzed conditions followed by epoxide cleavage with a propynyl aluminum reagent as key steps. The methodology was applied to the synthesis of the all-anti C6-C10 fragment of streptovaricin U. PMID:19236033

  20. Concise formal synthesis of (-)-salinosporamide A (marizomib) using a regio- and stereoselective epoxidation and reductive oxirane ring-opening strategy.

    PubMed

    Ling, Taotao; Potts, Barbara C; Macherla, Venkat R

    2010-06-04

    Expedient access to a highly functionalized 2-pyrrolidinone (8), the gamma-lactam core of 20S proteasome inhibitor (-)-salinosporamide A (marizomib; NPI-0052; 1), using a regio- and stereoselective epoxide formation/reductive oxirane ring-opening strategy is presented. Notably, the sequential construction of the C-4, C-3, and C-2 stereocenters of 1 in a completely stereocontrolled fashion is a key feature of streamlining the synthesis of intermediate 12. A related strategy is also discussed.

  1. Stereoselective synthesis of MLN4924, an inhibitor of NEDD8-activating enzyme.

    PubMed

    Lee, Hyuk Woo; Nam, Soo Kyung; Choi, Won Jun; Kim, Hea Ok; Jeong, Lak Shin

    2011-05-06

    MLN4924 (1), which is in clinical trials as an anticancer agent, was stereoselectively synthesized from d-ribose via a route involving stereoselective reduction, regioselective cleavage of an isopropylidene moiety, and selective displacement of a cyclic sulfate moiety as key steps.

  2. General, stereoselective synthesis of (Z)-beta,gamma-unsaturated nitriles promoted by samarium diiodide.

    PubMed

    Concellón, José M; Rodríguez-Solla, Humberto; Simal, Carmen; Santos, David; Paz, Nieves R

    2008-10-16

    A method to obtain (Z)-beta,gamma-unsaturated nitriles in high or good yields and with moderate or high stereoselectivity is described. The products were achieved through the photoinduced metalation of 3-acetoxy-4-chloronitriles with SmI2. The starting compounds were readily prepared, and a mechanism is proposed to explain this stereoselective beta-elimination reaction.

  3. Nucleophilic addition of organozinc reagents to 2-sulfonyl cyclic ethers: stereoselective synthesis of manassantins A and B.

    PubMed

    Kim, Hyoungsu; Kasper, Amanda C; Moon, Eui Jung; Park, Yongho; Wooten, Ceshea M; Dewhirst, Mark W; Hong, Jiyong

    2009-01-01

    A convergent route to the synthesis of manassantins A and B, potent inhibitors of HIF-1, is described. Central to the synthesis is a stereoselective addition of an organozinc reagent to a 2-benzenesulfonyl cyclic ether to achieve the 2,3-cis-3,4-trans-4,5-cis-tetrahydrofuran of the natural products. Preliminary structure-activity relationships suggested that the (R)-configuration at C-7 and C-7''' is not critical for HIF-1 inhibition. In addition, the hydroxyl group at C-7 and C-7''' can be replaced with a carbonyl group without loss of activity.

  4. Tunable Approach for the Stereoselective Synthesis of 1-C-Diethylphosphono(difluoromethyl) Iminosugars as Glycosyl Phosphate Mimics.

    PubMed

    Cocaud, Chloé; Nicolas, Cyril; Poisson, Thomas; Pannecoucke, Xavier; Legault, Claude Y; Martin, Olivier R

    2017-03-03

    An efficient methodology for the stereoselective and tunable addition of LiCF2P(O)(OEt)2 and BrMgCF2P(O)(OEt)2 reagents to N-t-butanesulfinyl glycosylamines is described with details on the stereochemical effects at play in this process. It provides a practical route to various 1-C-diethylphosphono(difluoromethyl) iminosugars as glycosyl phosphate and sugar nucleotide mimics.

  5. Stereoselective synthesis of C18-guggultetrol and C18-phytosphingosine analogues from D-fructose.

    PubMed

    Ramu Sridhar, Perali; Suresh, Mandava; Venu Kumar, Patteti; Seshadri, Kalapati; Venkata Rao, Chunduri

    2012-10-01

    A series of C(18)-guggultetrol stereo isomers and C(18)-phytosphingosine regio/stereo isomers were synthesised in a stereoselective fashion involving metal mediated fragmentation, stereoselective reduction, 1,4 O → O silyl migration, and Grubbs' cross metathesis as key steps. d-Fructose was used as a raw material for the preparation of all the analogues. The isophytosphingosine derivatives were evaluated against their 5-LOX (5-lipoxigenase) inhibitory activity.

  6. Dihydroxylation of 2-vinylaziridine: efficient synthesis of D-ribo-phytosphingosine.

    PubMed

    Yoon, Hyo Jae; Kim, Yong-Woo; Lee, Baeck Kyoung; Lee, Won Koo; Kim, Yongeun; Ha, Hyun-Joon

    2007-01-07

    An efficient and highly stereoselective synthesis of D-ribo-(2S,3S,4R)-phytosphingosine was accomplished in 62% overall yield starting from commercially available (2S)-hydroxymethylaziridine via osmium-catalyzed asymmetric dihydroxylation as a key step.

  7. Tuning the stereoelectronic properties of 1-sulfanylhex-1-enitols for the sequential stereoselective synthesis of 2-deoxy-2-iodo-β-D-allopyranosides.

    PubMed

    Kövér, Andrea; Boutureira, Omar; Matheu, M Isabel; Díaz, Yolanda; Castillón, Sergio

    2014-04-04

    The preparation of challenging 2-deoxy-2-iodo-β-D-allo precursors of 2-deoxy-β-D-ribo-hexopyranosyl units and other analogues is reported using a robust olefination-cyclization-glycosylation sequence. Here, we particularly focus on tuning the stereoelectronic properties of the alkenyl sulfides intermediates in order to improve the diastereoselectivity of the cyclization step and, hence, the efficiency of the overall transformation. Phosphine oxides with the general formula Ph2P(O)CH2SR (R = t-Bu, Cy, p-MeOPh, 2,6-di-ClPh, and 2,6-di-MePh) were easily synthesized and subsequently used in the olefination reaction with 2,3,5-tri-O-benzyl-D-ribose and -D-arabinose. The corresponding sugar-derived alkenyl sulfides were submitted to a 6-endo [I(+)]-induced cyclization, and the resulting 2-deoxy-2-iodohexopyranosyl-1-thioglycosides were used as glycosyl donors for the stereoselective synthesis of 2-deoxy-2-iodohexopyranosyl glycosides. Among the different S-groups studied, t-Bu derivative was the best performer for the synthesis of cholesteryl 2-deoxy-2-iodomannopyranosides, whereas for the synthesis of 2-deoxy-2-iodoallopyranosides none of the derivatives here studied proved superior to the phenyl analogue previously described. Glycosylation of cholesterol with different d-allo and d-manno derivatives produced 2-deoxy-2-iodoglycosides with stereoselectivities in the same order in each case, reinforcing the involvement of an oxocarbenium ion as the common intermediate of this crucial glycosylation step.

  8. Stereoselective Synthesis of 1,3-Diaminotruxillic Acid Derivatives: An Advantageous Combination of C-H-ortho-Palladation and On-Flow [2+2]-Photocycloaddition in Microreactors.

    PubMed

    Serrano, Elena; Juan, Alberto; García-Montero, Angel; Soler, Tatiana; Jiménez-Márquez, Francisco; Cativiela, Carlos; Gomez, M Victoria; Urriolabeitia, Esteban P

    2016-01-04

    The stereoselective synthesis of ε-isomers of dimethyl esters of 1,3-diaminotruxillic acid in three steps is reported. The first step is the ortho-palladation of (Z)-2-aryl-4-aryliden-5(4H)-oxazolones 1 to give dinuclear complexes 2 with bridging carboxylates. The reaction occurs through regioselective activation of the ortho-CH bond of the 4-arylidene ring in carboxylic acids. The second step is the [2+2]-photocycloaddition of the CC exocyclic bonds of the oxazolone skeleton in 2 to afford the corresponding dinuclear ortho-palladated cyclobutanes 3. This key step was performed very efficiently by using LED light sources with different wavelengths (465, 525 or 625 nm) in flow microreactors. The final step involved the depalladation of 3 by hydrogenation in methanol to afford the ε-1,3-diaminotruxillic acid derivatives as single isomers.

  9. Stereoselective Synthesis of Functionalized Bicyclic Scaffolds by Passerini 3‐Center‐2‐Component Reactions of Cyclic Ketoacids

    PubMed Central

    Cioc, Răzvan C.; Estévez, Verónica; van der Niet, Daan J.; Vande Velde, Christophe M. L.; Turrini, Nikolaus G.; Hall, Mélanie; Faber, Kurt

    2017-01-01

    We report the use of bifunctional starting materials (ketoacids) in a diastereoselective Passerini three‐center‐two‐component reaction. Study of the reaction scope revealed the required structural features for stereoselectivity in the isocyanide addition. In this system, an interesting isomerization of the primary Passerini product – the α‐carboxamido lactone – into an atypical product, an α‐hydroxy imide, was found to occur under acidic conditions. Furthermore, enantioenriched Passerini products can be generated from an enantioenriched ketoacid obtained by chemoenzymatic synthesis. PMID:28344504

  10. A very simple, highly stereoselective and modular synthesis of ferrocene-based P-chiral phosphine ligands.

    PubMed

    Chen, Weiping; Mbafor, William; Roberts, Stanley M; Whittall, John

    2006-03-29

    A very simple, highly stereoselective and modular synthesis of ferrocene-based P-chiral phosphine ligands has been developed. On the basis of this new methodology, several new families of ferrocene-based phosphine ligands have been prepared coupling chirality at phosphorus with other, more standard stereogenic features. The introduction of P-chirality into ferrocene-based phosphine ligands enhances the enantioselective discrimination produced by the corresponding Rh catalyst when a matching among the planar chirality, carbon chirality, and the chirality of phosphorus is achieved.

  11. On the Stereoselective Synthesis of (+)-Pinoresinol in Forsythia Suspensa from its Achiral Precursor, Coniferyl Alcohol

    NASA Technical Reports Server (NTRS)

    Davin, Laurence B.; Bedgar, Diana L.; Katayama, Takeshi; Lewis, Norman G.

    1992-01-01

    The residue from Forsythia suspensa stems, upon removal of soluble enzymes, has provided the first evidence for a stereoselective coupling enzyme in lignan biosynthesis. This preparation catalyses the preferred formation (ca 65%) of (+)-[8,8'- C-14] pinoresinol from [8-C-14]coniferyl alcohol in the absence of exogenously provided cofactors; addition of H2O2 had little effect on enantiomeric composition. However, when NAD and malate were supplied, the stereoselectivity of the coupling reaction was significantly enhanced and pinoresinol consisting of ca 80% of the (+)-antipode was obtained. Clearly, the insoluble residue contains a specific coupling enzyme which catalyses (+)-pinoresinol formation from coniferyl alcohol. By contrast, when [8- C-14] sinapyl alcohol was employed as substrate, only racemic syringaresinols were formed: this non-stereoselective peroxidase-catalysed coupling reaction presumably accounts for the low levels of (-)-pinoresinol encountered in this system when coniferyl alcohol is used as a substrate.

  12. Stereoselective synthesis of 3,3-diarylacrylonitriles as tubulin polymerization inhibitors.

    PubMed

    Fang, Zhenglai; Song, Yunlong; Sarkar, Taradas; Hamel, Ernest; Fogler, William E; Agoston, Gregory E; Fanwick, Phillip E; Cushman, Mark

    2008-06-06

    A series of 3,3-diarylacrylonitriles were synthesized stereoselectively as tubulin polymerization inhibitors for potential use in cancer chemotherapy. This synthetic route features stannylcupration and palladium-catalyzed Stille cross-coupling chemistry, allowing both E and Z isomers of 3,3-diarylacrylonitriles to be prepared in a very short sequence of reactions.

  13. Stereoselective synthesis and anti-inflammatory activities of 6- and 7-membered dioxacycloalkanes.

    PubMed

    Gu, Keli; Bi, Lanrong; Zhao, Ming; Wang, Chao; Dolan, Cheryl; Kao, Michael C; Tok, Jeffrey B-H; Peng, Shiqi

    2006-03-01

    A class of 5-trifluoroacetylamino-1,3-dioxacycloalkanes, 5-benzoylamino-1,3-dioxacycloalkanes, and 5-amino-1,3-dioxacycloalkane compounds were stereoselectively synthesized as potential anti-inflammatory drug candidates. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model, from which multiple compounds possessing anti-inflammatory properties which surpass aspirin were identified; these compounds were then compared to establish structure-activity relationships.

  14. Synthesis of 6'-branched locked nucleic acid by a radical TEMPO-scavanged stereoselective mercury cyclization.

    PubMed

    Enderlin, Gerald; Nielsen, Poul

    2008-09-05

    A 6'(R)-hydroxymethyl derivative of the locked nucleic acid (LNA)-thymidine monomer has been synthesized by a stereoselective mercury cyclization and subsequent use of TEMPO as a radical scavenger. This compound was converted to an azide derivative, which in a Huisgen-type [3 + 2] cycloaddition afforded a double-headed nucleoside with a triazole linking an additional thymine to the 6'-position of the LNA-nucleoside monomer.

  15. Directed functionalization of 1,2-dihydropyridines: stereoselective synthesis of 2,6-disubstituted piperidines.

    PubMed

    Pelletier, Guillaume; Constantineau-Forget, Léa; Charette, André B

    2014-07-04

    A practical and highly stereoselective approach to access 2,6-disubstituted piperidines using an amidine auxiliary is reported. Following the diastereoselective addition of Grignard reagents at the 2-position of an activated pyridinium salt, the amidine group directs a regioselective metalation at the 6-position, enabling further functionalization. A subsequent electrophilic quench or a Negishi cross-coupling could be performed, resulting in 2,6-disubstituted dihydropyridines. These were reduced to the saturated piperidine rings with high diastereoselectivity.

  16. Total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid via stereoselective C-H insertion and efficient 3,4-stereocontrol.

    PubMed

    Jung, Young Chun; Yoon, Cheol Hwan; Turos, Edward; Yoo, Kyung Soo; Jung, Kyung Woon

    2007-12-21

    Reported herein is a novel approach to the total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid, where the stereochemistries on C(2), C(3), and C(4) of the pyrrolidine core were introduced efficiently and selectively. A regio- and stereoselective C-H insertion reaction was utilized to prepare the gamma-lactam as an intermediate. A Michael-type cyclization of phenylsulfone with a conjugated acetylenic ketone was developed to prepare the tricyclic ketone as a key intermediate for (-)-alpha-kainic acid. Subsequently, a stereoselective dephenylsulfonylation was carried out successfully to secure the cis relationship at C(3) and C(4) centers. An unprecedented acetylation on the phenylsulfone, followed by a stereoselective dephenylsulfonylation, secured the trans relationship at C(3) and C(4) centers in (+)-alpha-allokainic acid.

  17. 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.

  18. Stereoselective synthesis of norephedrine and norpseudoephedrine by using asymmetric transfer hydrogenation accompanied by dynamic kinetic resolution.

    PubMed

    Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok

    2012-06-15

    Each of the enantiomers of both norephedrine and norpseudoephedrine were stereoselectively prepared from the common, prochiral cyclic sulfamidate imine of racemic 1-hydroxy-1-phenyl-propan-2-one by employing asymmetric transfer hydrogenation (ATH) catalyzed by the well-defined chiral Rh-complexes, (S,S)- or (R,R)-Cp*RhCl(TsDPEN), and HCO(2)H/Et(3)N as the hydrogen source. The ATH processes are carried out under mild conditions (rt, 15 min) and are accompanied by dynamic kinetic resolution.

  19. Wittig Reaction: Domino Olefination and Stereoselectivity DFT Study. Synthesis of the Miharamycins' Bicyclic Sugar Moiety.

    PubMed

    Cachatra, Vasco; Almeida, Andreia; Sardinha, João; Lucas, Susana D; Gomes, Ana; Vaz, Pedro D; Florêncio, M Helena; Nunes, Rafael; Vila-Viçosa, Diogo; Calhorda, Maria José; Rauter, Amélia P

    2015-11-20

    2-O-Acyl protected-d-ribo-3-uloses reacted with [(ethoxycarbonyl)methylene]triphenylphosphorane in acetonitrile to afford regio- and stereoselectively 2-(Z)-alkenes in 10-60 min under microwave irradiation. This domino reaction is proposed to proceed via tautomerization of 3-ulose to enol, acyl migration, tautomerization to the 3-O-acyl-2-ulose, and Wittig reaction. Alternatively, in chloroform, regioselective 3-olefination of 2-O-pivaloyl-3-uloses gave (E)-alkenes, key precursors for the miharamycins' bicyclic sugar moiety.

  20. Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene Carboetherification and Carboamination Reactions

    PubMed Central

    Wolfe, John P.

    2009-01-01

    The development of Pd-catalyzed carboetherification and carboamination reactions between aryl/alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of product formation, which involves an unusual intramolecular syn-insertion of an alkene into a Pd-Heteroatom bond is also discussed in detail. PMID:19183704

  1. Stereoselectivity in Polyphenol Biosynthesis

    NASA Technical Reports Server (NTRS)

    Lewis, Norman G.; Davin, Laurence B.

    1992-01-01

    Stereoselectivity plays an important role in the late stages of phenyl-propanoid metabolism, affording lignins, lignans, and neolignans. Stereoselectivity is manifested during monolignol (glucoside) synthesis, e.g., where the geometry (E or Z) of the pendant double bond affects the specificity of UDPG:coniferyl alcohol glucosyltransferases in different species. Such findings are viewed to have important ramifications in monolignol transport and storage processes, with roles for both E- and Z-monolignols and their glucosides in lignin/lignan biosynthesis being envisaged. Stereoselectivity is also of great importance in enantiose-lective enzymatic processes affording optically active lignans. Thus, cell-free extracts from Forsythia species were demonstrated to synthesize the enantiomerically pure lignans, (-)-secoisolariciresinol, and (-)-pinoresinol, when NAD(P)H, H2O2 and E-coniferyl alcohol were added. Progress toward elucidating the enzymatic steps involved in such highly stereoselective processes is discussed. Also described are preliminary studies aimed at developing methodologies to determine the subcellular location of late-stage phenylpropanoid metabolites (e.g., coniferyl alcohol) and key enzymes thereof, in intact tissue or cells. This knowledge is essential if questions regarding lignin and lignan tissue specificity and regulation of these processes are to be deciphered.

  2. Stereoselective synthesis of macrocyclic peptides via a dual olefin metathesis and ethenolysis approach.

    PubMed

    Mangold, Shane L; Grubbs, Robert H

    2015-08-01

    Macrocyclic compounds occupy an important chemical space between small molecules and biologics and are prevalent in many natural products and pharmaceuticals. The growing interest in macrocycles has been fueled, in part, by the design of novel synthetic methods to these compounds. One appealing strategy is ring-closing metathesis (RCM) that seeks to construct macrocycles from acyclic diene precursors using defined transition-metal alkylidene catalysts. Despite its broad utility, RCM generally gives rise to a mixture of E- and Z-olefin isomers that can hinder efforts for the large-scale production and isolation of such complex molecules. To address this issue, we aimed to develop methods that can selectively enrich macrocycles in E- or Z-olefin isomers using an RCM/ethenolysis strategy. The utility of this methodology was demonstrated in the stereoselective formation of macrocyclic peptides, a class of compounds that have gained prominence as therapeutics in drug discovery. Herein, we report an assessment of various factors that promote catalyst-directed RCM and ethenolysis on a variety of peptide substrates by varying the olefin type, peptide sequence, and placement of the olefin in macrocycle formation. These methods allow for control over olefin geometry in peptides, facilitating their isolation and characterization. The studies outlined in this report seek to expand the scope of stereoselective olefin metathesis in general RCM.

  3. Stereoselective synthesis of macrocyclic peptides via a dual olefin metathesis and ethenolysis approach

    PubMed Central

    Mangold, Shane L.

    2015-01-01

    Macrocyclic compounds occupy an important chemical space between small molecules and biologics and are prevalent in many natural products and pharmaceuticals. The growing interest in macrocycles has been fueled, in part, by the design of novel synthetic methods to these compounds. One appealing strategy is ring-closing metathesis (RCM) that seeks to construct macrocycles from acyclic diene precursors using defined transition-metal alkylidene catalysts. Despite its broad utility, RCM generally gives rise to a mixture of E- and Z-olefin isomers that can hinder efforts for the large-scale production and isolation of such complex molecules. To address this issue, we aimed to develop methods that can selectively enrich macrocycles in E- or Z-olefin isomers using an RCM/ethenolysis strategy. The utility of this methodology was demonstrated in the stereoselective formation of macrocyclic peptides, a class of compounds that have gained prominence as therapeutics in drug discovery. Herein, we report an assessment of various factors that promote catalyst-directed RCM and ethenolysis on a variety of peptide substrates by varying the olefin type, peptide sequence, and placement of the olefin in macrocycle formation. These methods allow for control over olefin geometry in peptides, facilitating their isolation and characterization. The studies outlined in this report seek to expand the scope of stereoselective olefin metathesis in general RCM. PMID:26509000

  4. Stereoselective synthesis of 1,3-disubstituted isoindolines via Rh(III)-catalyzed tandem oxidative olefination-cyclization of 4-aryl cyclic sulfamidates.

    PubMed

    Son, Se-Mi; Seo, Yeon Ji; Lee, Hyeon-Kyu

    2016-03-21

    Rh(III)-catalyzed tandem ortho C-H olefination of cyclic 4-aryl sulfamidates (1) and subsequent intramolecular cyclization are described. This reaction serves as a method for the direct and stereoselective synthesis of 1,3-disubstituted isoindolines (3) starting with enantiomerically enriched 4-aryl cyclic sulfamidates. In this process, the configurational integrity of the stereogenic center in the starting cyclic sulfamidate is completely retained. In addition, the process generates trans-1,3-disubstituted isoindolines exclusively.

  5. Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity

    PubMed Central

    Stavrinides, Anna; Tatsis, Evangelos C.; Caputi, Lorenzo; Foureau, Emilien; Stevenson, Clare E. M.; Lawson, David M.; Courdavault, Vincent; O'Connor, Sarah E.

    2016-01-01

    Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold. PMID:27418042

  6. Stereoselective synthesis of 2α-Chloropicropodophyllotoxins and insecticidal activity of their esters against oriental armyworm, Mythimna separata walker.

    PubMed

    Fan, Lingling; Guo, Yong; Zhi, Xiaoyan; Yu, Xiang; Xu, Hui

    2014-04-30

    As part of ongoing efforts to discover new natural-product-based insecticidal agents, in the present study, an efficient method for the stereoselective α-chlorination at the C-2 position of 2'(2',6')-(di)halogenopodophyllotoxin derivatives was first developed. Subsequently, a series of novel esters of 2α-chloro-2'(2',6')-(di)halogenopicropodophyllotoxin with modified C, D, and E rings of podophyllotoxin were smoothly obtained. Finally, all of the title compounds were tested against the pre-third-instar larvae of oriental armyworm (Mythimna separata Walker) at 1 mg/mL. It was found that besides their 2'-halogen-substituted E ring, the stereoselective α-chlorination at the C-2 position of 2'(2',6')-(di)halogenopodophyllotoxins was also related to the chlorination reagents. Especially 2α-chloro-4α-(benzoyl)oxy-2'-chloropicropodophyllotoxin (6e) and 2α-chloro-4α-(2-chlorophenylacyl)oxy-2'-bromopicropodophyllotoxin (8f) showed the most potent insecticidal activities, with final mortality rates of >60%. For 4α-(alkylacyl)oxy derivatives of 2α-chloro-2'(2',6')-(di)halogenopicropodophyllotoxin, the effect of the length of their side chain at the C-4 position of podophyllotoxin skeleton on the insecticidal activity was not very obvious. For 4α-(arylacyl)oxy derivatives of 2α-chloro-2'-chloro/bromopicropodophyllotoxin, an electronic effect of the substituents on their phenyl ring at the C-4 position of podophyllotoxin skeleton on the insecticidal activity was observed.

  7. Stereoselective Synthesis of α- and β-l-Ara4N Glycosyl H-Phosphonates and a Neoglycoconjugate Comprising Glycosyl Phosphodiester Linked β-l-Ara4N

    PubMed Central

    2016-01-01

    Stereoselective synthesis of variably protected α- and β-l-Ara4N glycosyl H-phosphonates as key intermediates in the syntheses of β-l-Ara4N-modified LPS structures and α-l-Ara4N-containing biosynthetic precursors is reported. A facile one-pot approach toward β-l-Ara4N glycosyl H-phosphonates includes anomeric deallylation of protected 4-azido β-l-Ara4N via terminal olefin isomerization followed by ozonolysis and methanolysis of formyl groups to furnish exclusively β-configured lactols that are phosphitylated with retention of configuration. The carbohydrate epitope of β-l-Ara4N-modified Lipid A, βGlcN(1→6)αGlcN(1→P←1)β-l-Ara4N, was stereoselectively synthesized and linked to maleimide-activated bovine serum albumin. PMID:28009171

  8. Regio- and Stereoselective Synthesis of Spiropyrrolizidines and Piperazines through Azomethine Ylide Cycloaddition Reaction.

    PubMed

    Haddad, Saoussen; Boudriga, Sarra; Porzio, François; Soldera, Armand; Askri, Moheddine; Knorr, Michael; Rousselin, Yoann; Kubicki, Marek M; Golz, Christopher; Strohmann, Carsten

    2015-09-18

    A series of original spiropyrrolizidine derivatives has been prepared by a one-pot three-component [3 + 2] cycloaddition reaction of (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones, l-proline, and the cyclic ketones 1H-indole-2,3-dione (isatin), indenoquinoxaline-11-one and acenaphthenequinone. We disclose an unprecedented isomerization of some spiroadducts leading to a new family of spirooxindolepyrrolizidines. Furthermore, these cycloadducts underwent retro-1,3-dipolar cycloaddition yielding unexpected regioisomers. Upon treatment of the dipolarophiles with in situ generated azomethine ylides from l-proline or acenaphthenequinone, formation of spiroadducts and unusual polycyclic fused piperazines through a stepwise [3 + 3] cycloaddition pathway is observed. The stereochemistry of these N-heterocycles has been confirmed by several X-ray diffraction studies. Some of these compounds exhibit extensive hydrogen bonding in the crystalline state. To enlighten the observed regio- and stereoselectivity of the [3 + 2] cycloaddition, calculations using the DFT approach at the B3LYP/6-31G(d,p) level were carried out. It was found that this reaction is under kinetic control.

  9. Lactones 42. Stereoselective enzymatic/microbial synthesis of optically active isomers of whisky lactone.

    PubMed

    Boratyński, Filip; Smuga, Małgorzata; Wawrzeńczyk, Czesław

    2013-11-01

    Two different methods, enzyme-mediated reactions and biotrasformations with microorganisms, were applied to obtain optically pure cis- and trans-isomers of whisky lactone 4a and 4b. In the first method, eight alcohol dehydrogenases were investigated as biocatalysts to enantioselective oxidation of racemic erythro- and threo-3-methyloctane-1,4-diols (1a and 1b). Oxidation processes with three of them, alcohol dehydrogenases isolated from horse liver (HLADH) as well as recombinant from Escherichia coli and primary alcohol dehydrogenase (PADH I), were characterized by the highest degree of conversion with moderate enantioselectivity (ee=27-82%) of the reaction. In all enzymatic reactions enantiomerically enriched not naturally occurring isomers of trans-(-)-(4R,5S)-4b or cis-(+)-(4R,5R)-4a were formed preferentially. In the second strategy, based on microbial lactonization of γ-oxoacids, naturally occurring opposite isomers of whisky lactones were obtained. Trans-(+)-(4S,5R)-isomer (ee=99%) of whisky lactone 4b was stereoselectively formed as the only product of biotransformations of 3-methyl-4-oxooctanoic acid (5) catalyzed by Didimospheria igniaria KCH6651, Laetiporus sulphurens AM525, Chaetomium sp.1 KCH6670 and Saccharomyces cerevisiae AM464. Biotransformation of γ-oxoacid 5, in the culture of Beauveria bassiana AM278 and Pycnidiella resinae KCH50 afforded a mixtures of trans-(+)-(4S,5R)-4b with enantiomeric excess ee=99% and cis-(-)-(4S,5S)-4a with enantiomeric excesses ee=77% and ee=45% respectively.

  10. Stereoselective Syntheses of Soman Analog

    DTIC Science & Technology

    1993-04-28

    AD-A283 855 AD_ _ _ _ CONTRACT NO: DAMDl7-88-C-8021 0 / TITLE: STEREOSELECTIVE SYNTHESES OF SOMAN ANALOG SUBTITLE: Synthesis of Pentacoordinate...SUPPLEMENTARY NOTES SUBTITLE: Synthesis of Pentacoordinate Phosphorus Compounds, "Bait and Switch" Compounds, and Soman Simulants as Hapten. for Production of...simulant. We reporit a detailed study on the synthesis , isolation and characterization of the four pure enantiomners; of [(S or R)-4 -amino-2,2-diniethyl-2

  11. Ru-catalyzed stereoselective addition of imides to alkynes.

    PubMed

    Goossen, Lukas J; Blanchot, Mathieu; Brinkmann, Claus; Goossen, Käthe; Karch, Ralph; Rivas-Nass, Andreas

    2006-12-08

    A catalyst system formed in situ from bis(2-methylallyl)cycloocta-1,5-dieneruthenium(II) ((cod)Ru[met]2), a phosphine, and scandium(III) trifluoromethanesulfonate (Sc(OTf)3) was found to efficiently catalyze the anti-Markovnikov addition of imides to terminal alkynes, allowing mild and atom-economic synthesis of enimides. Depending on the phosphine employed, both the (E)- and the (Z)-isomer can be accessed stereoselectively.

  12. Enzymatic synthesis of D-sorbose and D-psicose with aldolase RhaD: effect of acceptor configuration on enzyme stereoselectivity.

    PubMed

    Li, Zijie; Cai, Li; Qi, Qingsheng; Wang, Peng George

    2011-12-01

    It was previously reported that DHAP-dependent aldolase RhaD selectively chooses L-glyceraldehyde from racemic glyceraldehyde to produce l-fructose exclusively. Contrastingly, we discovered that D-glyceraldehyde is also tolerated as an acceptor and the stereoselectivity of the enzyme is lost in the corresponding aldol addition. Furthermore, we applied this property to efficiently synthesize two rare sugars D-sorbose and D-psicose.

  13. Regioselective reductive cleavage of bis-benzylidene acetal: stereoselective synthesis of anticancer agent OGT2378 and glycosidase inhibitor 1,4-dideoxy-1,4-imino-l-xylitol.

    PubMed

    Aravind, Appu; Sankar, Muthukumar Gomathi; Varghese, Babu; Baskaran, Sundarababu

    2009-04-03

    A highly regioselective reductive cleavage of the bis-benzylidene acetal of D-mannitol was performed using a BF(3) x Et(2)O/Et(3)SiH reagent system. A chiral intermediate 6 thus obtained was efficiently utilized in the stereoselective synthesis of the anticancer agent OGT2378 (3) and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol (22). Chemoselective reduction of azido epoxide 10 followed by regioselective intramolecular cyclization of amino epoxide 11 resulted in the exclusive formation of deoxyidonojirimycin derivative 12. By changing the order of deprotection, the chiral intermediate 6 was readily transformed to glycosidase inhibitor derivative 22.

  14. Stereoselective synthesis of substituted 1,3-oxazolidines via Pd-catalyzed carboamination reactions of O-vinyl-1,2-amino alcohols.

    PubMed

    Ward, Amanda F; Wolfe, John P

    2011-09-02

    The stereoselective synthesis of 2,4- and 2,5-disubstituted 1,3-oxazolidines is accomplished via Pd-catalyzed carboamination of O-vinyl-1,2-amino alcohol derivatives. The transformations generate cis-disubstituted products with good to excellent diastereoselectivity, and enantiomerically enriched substrates are converted without loss of optical purity. In addition to yielding synthetically useful products that are difficult to generate with existing methods, these transformations illustrate that electron-rich enol ethers are viable substrates for alkene carboamination processes.

  15. Stereoselective Synthesis of Quaternary Carbons via the Dianionic Ireland–Claisen Rearrangement

    PubMed Central

    2015-01-01

    A dianionic Ireland–Claisen rearrangement of chiral, nonracemic α-methyl-β-hydroxy allylic esters has been developed that proceeds with high diastereoselectivity and provides products containing three contiguous stereogenic carbons, including a quaternary center. The potential utility of the rearrangement for complex molecule synthesis is also demonstrated. PMID:24735235

  16. An efficient synthesis of loline alkaloids

    NASA Astrophysics Data System (ADS)

    Cakmak, Mesut; Mayer, Peter; Trauner, Dirk

    2011-07-01

    Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.

  17. Stereoselection in Intramolecular Diels-Alder Reactions of 2-Cyano-1-azadienes: Indolizidine and Quinolizidine Synthesis.

    PubMed

    Tay, Gidget C; Sizemore, Nicholas; Rychnovsky, Scott D

    2016-07-01

    Progress toward understanding the scope and diastereoselectivity of intramolecular Diels-Alder reactions using 2-cyano-1-azadienes is described herein. The resulting cyanoenamine products are underutilized intermediates in organic synthesis. Assembly of the Diels-Alder precursors was achieved using an improved imine condensation/oxidative cyanation protocol. By this method, several highly substituted indolizidine and quinolizidine architectures were constructed. Quantum mechanical DFT calculations at the B3LYP/6-31+G(d) level of theory were performed for these cyclizations and provide insights into the origins of the observed diastereoselectivities.

  18. Stereoselective synthesis of imidazolidin-2-ones via Pd-catalyzed alkene carboamination. Scope and limitations

    PubMed Central

    Fritz, Jonathan A.; Wolfe, John P.

    2008-01-01

    A method for the synthesis of imidazolidin-2-ones from N-allylureas and aryl or alkenyl bromides via Pd-catalyzed carboamination reactions is described. The N-allylurea precursors are prepared in one step from readily available allylic amines and isocyanates, and the Pd-catalyzed reactions effect the formation of a C–C bond, a C–N bond, and up to two stereocenters in a single step. Good diastereoselectivities are obtained for the conversion of substrates bearing allylic substituents to 4,5-disubstituted imidazolidin-2-ones, and excellent selectivity for the generation of products resulting from syn-addition across the alkene is observed when substrates derived from cyclic alkenes or E-1,2-disubstituted alkenes are employed. A brief discussion of reaction mechanism and product stereochemistry is presented. PMID:19122758

  19. Stereoselective synthesis of 3-methyleneisoindolin-1-ones via base-catalyzed intermolecular reactions of electron-deficient alkynes with N-hydroxyphthalimides.

    PubMed

    Chen, Xin; Ge, Fei-Fei; Lu, Tao; Zhou, Qing-Fa

    2015-03-20

    Highly stereoselective intermolecular reactions of electron-deficient alkynes with N-hydroxyphthalimides for efficient construction of N-unprotected 3-methyleneisoindolin-1-ones have been developed through base catalytic strategies. The reaction of alkynoates with N-hydroxyphthalimides catalyzed by Bu3P in DMF at 150 °C gave the corresponding 3-methyleneisoindolin-1-ones with a (Z)-configuration, while the reaction of alkynoates with N-hydroxyphthalimides catalyzed by K2CO3 in DMF at 60 °C gave the corresponding 3-methyleneisoindolin-1-ones with an (E)-configuration, and (Z)-3-methyleneisoindolin-1-ones were obtained when alkyne ketones reacted with N-hydroxyphthalimide.

  20. Stereoselective synthesis of 4-substituted-cyclic sulfamidate-5-carboxylates by asymmetric transfer hydrogenation accompanied by dynamic kinetic resolution and applications to concise stereoselective syntheses of (-)-epi-cytoxazone and the taxotere side-chain.

    PubMed

    Kim, Jin-ah; Seo, Yeon Ji; Kang, Soyeong; Han, Juae; Lee, Hyeon-Kyu

    2014-11-18

    Dynamic kinetic resolution driven, asymmetric transfer hydrogenation reactions of cyclic sulfamidate imine-5-carboxylate esters were developed. Applications of the new methodology to stereoselective syntheses of the taxotere side-chain and (-)-epi-cytoxazone are described.

  1. An Improved Helferich Method for the α/β-Stereoselective Synthesis of 4-Methylumbelliferyl Glycosides for the Detection of Microorganisms.

    PubMed

    Wei, Xianhu; Ma, Yanxia; Wu, Qingping; Zhang, Jumei; Cai, Zhihe; Lu, Mianfei

    2015-12-04

    An improved Helferich method is presented. It involves the glycosylation of 4-methyl-umbelliferone with glycosyl acetates in the presence of boron trifluoride etherate combined with triethylamine, pyridine, or 4-dimethylaminopyridine under mild conditions, followed by deprotection to give fluorogenic 4-methylumbelliferyl glycoside substrates. Due to the use of base, the glycosylation reaction proceeds more easily, is uncommonly α- or β-stereoselective, and affords the corresponding products in moderate to excellent yields (51%-94%) under appropriate conditions.

  2. Stereoselective synthesis, spectral and antimicrobial studies of some cyanoacetyl hydrazones of 3-alkyl-2,6-diarylpiperidin-4-ones

    NASA Astrophysics Data System (ADS)

    Velayutham Pillai, M.; Rajeswari, K.; Vidhyasagar, T.

    2014-11-01

    A series of novel cyanoacetyl hydrazones of 3-alkyl-2,6-diarylpiperidin-4-ones were synthesized stereoselectively and characterized by IR, Mass, 1H NMR, 13C NMR, 1H-1H COSY and 1H-13C COSY spectra. The stereochemistry of the synthesized compounds was established using NMR spectra. Antimicrobial screening of the synthesized compounds revealed their antibacterial and antifungal potencies. Growth inhibition of Enterobacter Aerogenes by compound 15 was found to be superior to the standard drug.

  3. Controlled synthesis of biodegradable lactide polymers and copolymers using novel in situ generated or single-site stereoselective polymerization initiators.

    PubMed

    Zhong, Zhiyuan; Dijkstra, Pieter J; Feijen, Jan

    2004-01-01

    Polylactides and their copolymers are key biodegradable polymers used widely in biomedical, pharmaceutical and ecological applications. The development of synthetic pathways and catalyst/initiator systems to produce pre-designed polylactides, as well as the fundamental understanding of the polymerization reactions, has continuously been an important topic. Here, we will address the recent advances in the ring-opening polymerization of lactides, with an emphasis on the highly versatile in situ generated initiator systems and single-site stereoselective initiators. The in situ generated initiators including in situ formed yttrium, calcium and zinc alkoxides all have been shown to bring about a rapid and living polymerization of lactides under mild conditions, which facilitated the preparation of a variety of advanced lactide-based biomaterials. For example, well-defined di- and tri-block copolymers consisting of hydrophilic poly(ethylene glycol) blocks and hydrophobic polyester blocks, which form novel biodegradable polymersomes or biodegradable thermosensitive hydrogels, have been prepared. In the past few years, significant progress has also been made in the area of stereoselective polymerization of lactides. This new generation of initiators has enabled the production of polylactide materials with novel microstructures and/or properties, such as heterotactic (--RRSSRRSSRRSS--) polylactide, crystalline syndiotactic (--RSRSRSRSRSRS--) polylactide and isotactic stereoblock (--Rn Sn Rn Sn--) polylactide, exhibiting a high melting temperature. The recently developed polymerizations using in situ generated initiators and stereoselective polymerizations have no doubt opened a brand-new avenue for the design and exploration of polylactides and their copolymers.

  4. Stereoselective synthesis of light-activatable perfluorophenylazide-conjugated carbohydrates for glycoarray fabrication and evaluation of structural effects on protein binding by SPR imaging.

    PubMed

    Deng, Lingquan; Norberg, Oscar; Uppalapati, Suji; Yan, Mingdi; Ramström, Olof

    2011-05-07

    A series of light-activatable perfluorophenylazide (PFPA)-conjugated carbohydrate structures have been synthesized and applied to glycoarray fabrication. The glycoconjugates were structurally varied with respect to anomeric attachment, S-, and O-linked carbohydrates, respectively, as well as linker structure and length. Efficient stereoselective synthetic routes were developed, leading to the formation of the PFPA-conjugated structures in good yields over few steps. The use of glycosyl thiols as donors proved especially efficient and provided the final compounds in up to 70% total yield with high anomeric purities. PFPA-based photochemistry was subsequently used to generate carbohydrate arrays on a polymeric surface, and surface plasmon resonance imaging (SPRi) was applied for evaluation of carbohydrate-protein interactions using the plant lectin Concanavalin A (Con A) as a probe. The results indicate better performance and equal efficiency of S- and O-linked structures with intermediate linker length.

  5. A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids.

    PubMed

    Kia, Yalda; Osman, Hasnah; Kumar, Raju Suresh; Murugaiyah, Vikneswaran; Basiri, Alireza; Perumal, Subbu; Razak, Ibrahim Abdul

    2013-05-15

    A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13μM, respectively.

  6. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

    PubMed Central

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold

    2016-01-01

    Summary Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

  7. Stereoselective Synthesis of 8,12-Furanoeudesmanes from Santonin. Absolute Stereochemistry of Natural Furanoeudesma-1,3-diene and Tubipofurane.

    PubMed

    Blay, Gonzalo; Cardona, Luz; García, Begoña; Pedro, José R.; Sánchez, Juan J.

    1996-05-31

    Ketobutenolide 3, easily obtained from santonin (1), has been transformed into two natural furanoeudesmanes 4 and 5, isolated from Commiphora molmol and Tubipora musica, respectively. trans- And cis-decalin systems were obtained by stereoselective reduction of the C(4)-C(5) double bond in 3 in the following way: hydrogenation of 3 over Pd/C followed by acidic treatment gave the cis isomer 10 as the major product; selective hydrogenation of the C(1)-C(2) double bond with the Wilkinson's catalyst followed by reduction with NaTeH yielded mainly the trans isomer 9. Compounds 9 and 10 were transformed into 4 and 5 in parallel sequences. Optical rotation and CD measurements of the synthetic products revealed that the stereochemistry of both natural products should be revised to their enantiomeric form.

  8. Chemical synthesis of two series of nerve agent model compounds and their stereoselective interaction with human acetylcholinesterase and human butyrylcholinesterase.

    PubMed

    Barakat, Nora H; Zheng, Xueying; Gilley, Cynthia B; MacDonald, Mary; Okolotowicz, Karl; Cashman, John R; Vyas, Shubham; Beck, Jeremy M; Hadad, Christopher M; Zhang, Jun

    2009-10-01

    Both G and V type nerve agents possess a center of chirality about phosphorus. The S(p) enantiomers are generally more potent inhibitors than their R(p) counterparts toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To develop model compounds with defined centers of chirality that mimic the target nerve agent structures, we synthesized both the S(p) and the R(p) stereoisomers of two series of G type nerve agent model compounds in enantiomerically enriched form. The two series of model compounds contained identical substituents on the phosphorus as the G type agents, except that thiomethyl (CH(3)-S-) and thiocholine [(CH(3))(3)NCH(2)CH(2)-S-] groups were used to replace the traditional nerve agent leaving groups (i.e., fluoro for GB, GF, and GD and cyano for GA). Inhibition kinetic studies of the thiomethyl- and thiocholine-substituted series of nerve agent model compounds revealed that the S(p) enantiomers of both series of compounds showed greater inhibition potency toward AChE and BChE. The level of stereoselectivity, as indicated by the ratio of the bimolecular inhibition rate constants between S(p) and R(p) enantiomers, was greatest for the GF model compounds in both series. The thiocholine analogues were much more potent than the corresponding thiomethyl analogues. With the exception of the GA model compounds, both series showed greater potency against AChE than BChE. The stereoselectivity (i.e., S(p) > R(p)), enzyme selectivity, and dynamic range of inhibition potency contributed from these two series of compounds suggest that the combined application of these model compounds will provide useful research tools for understanding interactions of nerve agents with cholinesterase and other enzymes involved in nerve agent and organophosphate pharmacology. The potential of and limitations for using these model compounds in the development of biological therapeutics against nerve agent toxicity are also discussed.

  9. Large-scale synthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate by a stereoselective carbonyl reductase with high substrate concentration and product yield.

    PubMed

    Liu, Zhi-Qiang; Hu, Zhong-Liang; Zhang, Xiao-Jian; Tang, Xiao-Ling; Cheng, Feng; Xue, Ya-Ping; Wang, Ya-Jun; Wu, Lin; Yao, Dan-Kai; Zhou, Yi-Teng; Zheng, Yu-Guo

    2017-03-07

    To biosynthesize the (3R,5S)-CDHH in an industrial scale, a newly synthesized stereoselective short chain carbonyl reductase (SCR) was successfully cloned and expressed in Escherichia coli. The fermentation of recombinant E. coli harboring SCR was carried out in 500 L and 5000 L fermenters, with biomass and specific activity of 9.7 g DCW/L, 15749.95 U/g DCW, and 10.97 g DCW/L, 19210.12 U/g DCW, respectively. The recombinant SCR was successfully applied for efficient production of (3R,5S)-CDHH. The scale-up synthesis of (3R,5S)-CDHH was performed in 5000 L bioreactor with 400 g/L of (S)-CHOH at 30°C, resulting in a space-time yield of 13.7 mM/h/g DCW, which was the highest ever reported. After isolation and purification, the yield and d.e. of (3R,5S)-CDHH reached 97.5% and 99.5%, respectively. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 2017.

  10. Stereoselectivity in drug metabolism.

    PubMed

    Lu, Hong

    2007-04-01

    Many chiral drugs are used as their racemic mixtures in clinical practice. Two enantiomers of a chiral drug generally differ in pharmacodynamic and/or pharmacokinetic properties as a consequence of the stereoselective interaction with optically active biological macromolecules. Thus, a stereospecific assay to discriminate between enantiomers is required in order to relate plasma concentrations to pharmacological effect of a chiral drug. Stereoselective metabolism of drugs is most commonly the major contributing factor to stereoselectivity in pharmacokinetics. Metabolizing enzymes often display a preference for one enantiomer of a chiral drug over the other, resulting in enantioselectivity. The structural characteristics of enzymes dictate the enantiomeric discrimination associated with the metabolism of chiral drugs. The stereoselectivity can, therefore, be viewed as the physical property characteristic that phenotypes the enzyme. This review provides a comprehensive appraisal of stereochemical aspects of drug metabolism (i.e., enantioselective metabolism and first-pass effect, enzyme-selective inhibition or induction and drug interaction, species differences and polymorphic metabolism).

  11. A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities.

    PubMed

    Bharkavi, Chelliah; Vivek Kumar, Sundaravel; Ashraf Ali, Mohamed; Osman, Hasnah; Muthusubramanian, Shanmugam; Perumal, Subbu

    2016-11-15

    A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.

  12. Indium-Mediated Stereoselective Allylation.

    PubMed

    Kumar, Dinesh; Vemula, Sandeep R; Balasubramanian, Narayanaganesh; Cook, Gregory R

    2016-10-04

    Stereoselective indium-mediated organic reactions have enjoyed tremendous growth in the last 25 years. This is in part due to the insensitivity of allylindium to moisture, affording facile and practical reaction conditions coupled with outstanding functional group tolerance and minimal side reactions. Despite the plethora of articles about allylindium, there is much yet to be discovered and exploited for efficient and sustainable synthesis. In this Account, we describe indium-mediated synthetic methods for the preparation of chiral amines with the aim to present a balance of practical method development, novel asymmetric chemistry, and mechanistic understanding that impact multiple chemical and materials science disciplines. In 2005, we demonstrated the indium-mediated allylation of chiral hydrazones with complete diastereoselectivity (>99:1) and quantitative yields. Further, we revealed the first example of enantioselective indium-mediated allylation of hydrazones using catalytic (R)-3,3'-bis(trifluoromethyl)-BINOL ligands to afford homoallylic amines with high enantioselectivity. The use of enantiopure perfluoroalkylsulfonate BINOLs greatly improved the indium-mediated allylation of N-acylhydrazones with exquisite enantiocontrol (99% yield, 99% ee). This laboratory has also investigated indium-mediated asymmetric intramolecular cyclization in the presence of amino acid additives to deliver biologically relevant chromanes with excellent diastereoselectivity (dr >99:1). The effect of amino acid additives (N-Boc-glycine) was further investigated during the indium-mediated allylation of isatins with allyl bromide to yield homoallylic alcohols in excellent yields in a short time with a wide range of functional group tolerance. Critical mechanistic insight was gained, and evidence suggests that the additive plays two roles: (1) to increase the rate of formation of allylindium from allyl bromide and In(0) and (2) to increase the nucleophilicity of the allylindium

  13. The Evans Aldol-Prins cyclization: a general and stereoselective method for the synthesis of 2,3,4,5,6-pentasubstituted tetrahydropyrans.

    PubMed

    Álvarez-Méndez, Sergio J; García, Celina; Martín, Víctor S

    2016-02-25

    A general and stereoselective method to synthesize 2,3,4,5,6-pentasubstituted tetrahydropyrans in three steps starting from three different aldehydes is described. Key substrates β,γ-unsaturated N-acyloxazolidin-2-ones were subjected to an "Evans Aldol-Prins" protocol to generate five σ-bonds and five stereocenters in only a one-pot process with yields up to 60% and excellent stereoselectivities.

  14. Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

    PubMed Central

    Brenna, Davide; Massolo, Elisabetta; Puglisi, Alessandra; Rossi, Sergio; Celentano, Giuseppe; Capriati, Vito

    2016-01-01

    Different deep eutectic solvent (DES) mixtures were studied as reaction media for the continuous synthesis of enantiomerically enriched products by testing different experimental set-ups. L-Proline-catalysed cross-aldol reactions were efficiently performed in continuo, with high yield (99%), anti-stereoselectivity, and enantioselectivity (up to 97% ee). Moreover, using two different DES mixtures, the diastereoselectivity of the process could be tuned, thereby leading to the formation, under different experimental conditions, to both the syn- and the anti-isomer with very high enantioselectivity. The excess of cyclohexanone was recovered and reused, and the reaction could be run and the product isolated without the use of any organic solvent by a proper choice of DES components. The dramatic influence of the reaction media on the reaction rate and stereoselectivity of the process suggests that the intimate architecture of DESs deeply influences the reactivity of different species involved in the catalytic cycle. PMID:28144332

  15. Organocatalytic azomethine imine-olefin click reaction: high-yielding stereoselective synthesis of spiroindane-1,3-dione-pyrazolidinones.

    PubMed

    Ramachary, Dhevalapally B; Prabhakar Reddy, T; Suresh Kumar, A

    2016-07-06

    In search of developing new useful "click reactions", herein we report the organocatalytic azomethine imine-olefin [3 + 2]-cycloaddition as a new click reaction for the synthesis of drug-like spiroindane-1,3-dione-pyrazolidinones from indane-1,3-diones, aldehydes and N,N-cyclic azomethine imines through amino acid-catalysis. The scope of this new click reaction is demonstrated using many examples with high reactivity, selectivity and yields.

  16. Stereoselective synthesis of 1,3-anti diols by an Ipc-mediated domino aldol-coupling/reduction sequence.

    PubMed

    Dieckmann, Michael; Menche, Dirk

    2013-01-04

    A novel domino process for 1,3-anti diol synthesis by the union of a methyl ketone with an aldehyde is described. The operationally simple procedure is based on an Ipc-boron-aldol coupling and subsequent Ipc-mediated reduction of the intermediate β-hydroxy-ketone. The sequence proceeds with excellent anti-selectivities and enables the rapid construction of complex polyketide fragments.

  17. [Development of highly stereoselective reactions utilizing heteroatoms--new approach to the stereoselective Horner-Wadsworth-Emmons reaction].

    PubMed

    Sano, S

    2000-05-01

    This article reviews a new approach to stereoselective Horner-Wadsworth-Emmons (HWE) reactions. The HWE reaction is one of the most efficient methods for the preparation of alpha,beta-unsaturated esters, which play an important role in the synthesis of biologically active compounds. The reactions of aldehydes with phosphonates bearing alpha-substituents which stabilize the carbanion, preferentially furnish the corresponding E-alkenes. However, the stereoselectivity of the HWE reactions with ketones has never been investigated in detail because of their low reactivity and low stereoselectivity. The conventional HWE reactions of aryl alkyl ketones with ethyl diethylphosphonoacetate in the presence of sodium hydride gave the corresponding alpha,beta-unsaturated esters with modest E-selectivity. On the other hand, the treatment of aryl alkyl ketones with ethyl diethylphosphonoacetate in the presence of Sn(OSO2CF3)2 and N-ethylpiperidine afforded alpha,beta-unsaturated esters in a highly Z-selective fashion. A significant improvement in the selectivity and yield was found when the Still's reagent, methyl bis(trifluoroethyl)phosphonoacetate, was used under Sn(II)-mediated conditions. On the basis of the experimental results, the high Z-selectivity in the Sn(II)-mediated HWE reactions of aryl alkyl ketones with these phosphonates can be rationalized in terms of six-membered transition state involving Sn(II) chelation. Similarly, the HWE reactions of aryl alkyl ketones with ethyl 2-fluoro-2-diethylphosphonoacetate in the presence of Sn(OSO2CF3)2 and N-ethylpiperidine gave the corresponding alpha-fluoro-alpha,beta-unsaturated esters in a highly E-selective manner. Finally, the Sn(II)-mediated asymmetric HWE reactions of isopropyl 2-fluoro-2-diethylphosphonoacetate with 4-tert-butylcyclohexanone in the presence of a chiral diamine is described.

  18. Organocatalytic Synthesis of Higher‐Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d‐Glycero‐l‐galacto‐oct‐2‐ulose†

    PubMed Central

    Popik, Oskar; Pasternak‐Suder, Monika; Baś, Sebastian

    2015-01-01

    Abstract Herein we report a short and efficient protocol for the synthesis of naturally occurring higher‐carbon sugars—sedoheptulose (d‐altro‐hept‐2‐ulose) and d‐glycero‐l‐galacto‐oct‐2‐ulose—from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn‐selective aldol reaction of DHA with d‐erythrose and d‐xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn‐selective carbon–carbon‐bond‐forming aldol reactions promoted by primary‐based organocatalysts. For example, this methodology provided useful access to d‐glycero‐d‐galacto‐oct‐2‐ulose and 1‐deoxy‐d‐glycero‐d‐galacto‐oct‐2‐ulose from d‐arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1). PMID:27308197

  19. Tactical Synthesis Of Efficient Global Search Algorithms

    NASA Technical Reports Server (NTRS)

    Nedunuri, Srinivas; Smith, Douglas R.; Cook, William R.

    2009-01-01

    Algorithm synthesis transforms a formal specification into an efficient algorithm to solve a problem. Algorithm synthesis in Specware combines the formal specification of a problem with a high-level algorithm strategy. To derive an efficient algorithm, a developer must define operators that refine the algorithm by combining the generic operators in the algorithm with the details of the problem specification. This derivation requires skill and a deep understanding of the problem and the algorithmic strategy. In this paper we introduce two tactics to ease this process. The tactics serve a similar purpose to tactics used for determining indefinite integrals in calculus, that is suggesting possible ways to attack the problem.

  20. Synthesis of Differentially Protected myo- and chiro-Inositols from D-Xylose; Stereoselectivity in Intramolecular SmI2-Promoted Pinacol Reactions

    PubMed Central

    Luchetti, Giovanni; Ding, Kejia

    2009-01-01

    Methods for the enantioselective conversion of D-xylose to differentially protected myo-inositol and L-chiro-inositol have been developed. The key transformation is a highly diastereoselective intramolecular SmI2-promoted pinacol coupling. The stereoselectivity was extremely dependent on the conditions, suggesting a change in mechanism. Preliminary mechanistic experiments and possible explanations for this behavior are discussed. PMID:20622936

  1. Regioselective SN2' Mitsunobu reaction of Morita-Baylis-Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives.

    PubMed

    Xu, Silong; Shang, Jian; Zhang, Junjie; Tang, Yuhai

    2014-01-01

    A highly regioselective SN2' Mitsunobu reaction between Morita-Baylis-Hillman (MBH) alcohols, azodicarboxylates, and triphenylphosphine is developed, which provides an easy access to α-alkylidene-β-hydrazino acid derivatives in high yields and good stereoselectivity. This reaction represents the first direct transformation of MBH alcohols into hydrazines.

  2. Controllable stereoselective synthesis of trisubstituted alkenes by a catalytic three-component reaction of terminal alkynes, benzylic alcohols, and simple arenes.

    PubMed

    Li, Hai-Hua; Jin, Yin-Huan; Wang, Jie-Qi; Tian, Shi-Kai

    2009-08-21

    The acid-catalyzed three-component reaction of terminal alkynes, benzylic alcohols, and simple arenes provides convenient and atom-economic access to an array of both Z- and E-isomers of trisubstituted alkenes with excellent stereoselectivity by switching reaction temperature and acidic catalysts.

  3. Cobalt(II)-catalyzed 1,4-addition of organoboronic acids to activated alkenes: an application to highly cis-stereoselective synthesis of aminoindane carboxylic acid derivatives.

    PubMed

    Chen, Min-Hsien; Mannathan, Subramaniyan; Lin, Pao-Shun; Cheng, Chien-Hong

    2012-11-19

    It all adds up: The 1,4-addition of organoboronic acids to activated alkenes catalyzed by [Co(dppe)Cl(2)] is described. A [3+2]-annulation reaction of ortho-iminoarylboronic acids with acrylates to give various aminoindane carboxylic acid derivatives with cis-stereoselectivity is also demonstrated (see scheme; dppe = 1,2-bis(diphenylphosphino)ethane).

  4. Redesigning Aldolase Stereoselectivity by Homologous Grafting

    PubMed Central

    Henßen, Birgit; Metz, Alexander; Gohlke, Holger; Pietruszka, Jörg

    2016-01-01

    The 2-deoxy-d-ribose-5-phosphate aldolase (DERA) offers access to highly desirable building blocks for organic synthesis by catalyzing a stereoselective C-C bond formation between acetaldehyde and certain electrophilic aldehydes. DERA´s potential is particularly highlighted by the ability to catalyze sequential, highly enantioselective aldol reactions. However, its synthetic use is limited by the absence of an enantiocomplementary enzyme. Here, we introduce the concept of homologous grafting to identify stereoselectivity-determining amino acid positions in DERA. We identified such positions by structural analysis of the homologous aldolases 2-keto-3-deoxy-6-phosphogluconate aldolase (KDPG) and the enantiocomplementary enzyme 2-keto-3-deoxy-6-phosphogalactonate aldolase (KDPGal). Mutation of these positions led to a slightly inversed enantiopreference of both aldolases to the same extent. By transferring these sequence motifs onto DERA we achieved the intended change in enantioselectivity. PMID:27327271

  5. Efficient synthesis of highly substituted tetrahydroindazolone derivatives.

    PubMed

    Scala, Angela; Piperno, Anna; Risitano, Francesco; Cirmi, Santa; Navarra, Michele; Grassi, Giovanni

    2015-08-01

    A straightforward and efficient method for the synthesis of novel highly substituted and diversely functionalized indazolone derivatives has been developed. The transformation consists of a cyclocondensation of selected 1,3,3'-tricarbonyls with monosubstituted hydrazines. The starting β-triketones were prepared by an efficient chemo- and regioselective method under MW irradiation, exploiting the oxazolone chemistry. The reaction is easily accomplished under mild conditions and appears versatile, providing a synthetic diversification method with potential for drug-like compounds preparation.

  6. An efficient catalytic method for fulvene synthesis

    PubMed Central

    Coşkun, Necdet; Erden, Ihsan

    2011-01-01

    The effects of the nature and amount of base, substrate structure, amount of added water and solvent on the condensation of carbonyl compounds with cyclopentadiene in the presence of secondary amines were investigated. Based on these studies, a new efficient and green synthesis of fulvenes was developed. PMID:22021940

  7. Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

    PubMed Central

    Westphal, Julia C

    2014-01-01

    Summary A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide. PMID:24605158

  8. Efficient Biocatalytic Synthesis of Chiral Chemicals.

    PubMed

    Zhang, Zhi-Jun; Pan, Jiang; Ma, Bao-Di; Xu, Jian-He

    2016-01-01

    Chiral chemicals are a group of important chiral synthons for the synthesis of a series of pharmaceuticals, agrochemicals, and fine chemicals. In past decades, a number of biocatalytic approaches have been developed for the green and effective synthesis of various chiral chemicals. However, the practical application of these biocatalytic processes is still hindered by the lack of highly efficient and robust biocatalysts, which usually results in the low volumetric productivity and high cost of the bioprocesses. Further step forward of biocatalysis in industrial application strongly requires the development of versatile and highly efficient biocatalysts, aiming to increase the process efficiency and facilitate the downstream processing. Recently, the fast growth of genome sequences in the database in post-genomic era offers great opportunities for accessing numerous biocatalysts with practical application potential, and the so-called genome mining approach provides time-effective and highly specific strategy for the fast identification of target enzymes with desired properties and outperforms the traditional screening of soil samples for microbial enzyme producers of interest. A number of biocatalytic processes with industrial application potential were developed thereafter. Further development of protein engineering strategies, process optimization, and cooperative work between biologists, organic chemists, and engineers is expected to make biocatalysis technology the first choice approach for the eco-friendly, highly efficient, and cost-effective synthesis of chiral chemicals in the near future.

  9. Stereoselective Synthesis of 4-Substituted Cyclic Sulfamidate-5-Phosphonates by Using Rh-Catalyzed, Asymmetric Transfer Hydrogenation with Accompanying Dynamic Kinetic Resolution.

    PubMed

    Seo, Yeon Ji; Kim, Jin-ah; Lee, Hyeon-Kyu

    2015-09-04

    Dynamic kinetic resolution driven, asymmetric transfer hydrogenation of 4-substituted cyclic sulfamidate imine-5-phosphonates produces the corresponding cyclic sulfamidate-5-phosphonates. The process employs a HCO2H/Et3N mixture as the hydrogen source and the chiral Rh catalysts, (R,R)- or (S,S)-Cp*RhCl(TsDPEN), and it takes place at room temperature within 1 h with high yields and high levels of stereoselectivity.

  10. One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular SN2 reaction.

    PubMed

    Xiong, Yiwen; Qian, Ping; Cao, Chenhui; Mei, Haibo; Han, Jianlin; Li, Guigen; Pan, Yi

    2014-01-01

    We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) .

  11. On-chip integration of organic synthesis and HPLC/MS analysis for monitoring stereoselective transformations at the micro-scale.

    PubMed

    Heiland, Josef J; Warias, Rico; Lotter, Carsten; Mauritz, Laura; Fuchs, Patrick J W; Ohla, Stefan; Zeitler, Kirsten; Belder, Detlev

    2016-12-20

    We present a microfluidic system, seamlessly integrating microflow and microbatch synthesis with a HPLC/nano-ESI-MS functionality on a single glass chip. The microfluidic approach allows to efficiently steer and dispense sample streams down to the nanoliter-range for studying reactions in quasi real-time. In a proof-of-concept study, the system was applied to explore amino-catalyzed reactions, including asymmetric iminium-catalyzed Friedel-Crafts alkylations in microflow and micro confined reaction vessels.

  12. Approximation concepts for efficient structural synthesis

    NASA Technical Reports Server (NTRS)

    Schmit, L. A., Jr.; Miura, H.

    1976-01-01

    It is shown that efficient structural synthesis capabilities can be created by using approximation concepts to mesh finite element structural analysis methods with nonlinear mathematical programming techniques. The history of the application of mathematical programming techniques to structural design optimization problems is reviewed. Several rather general approximation concepts are described along with the technical foundations of the ACCESS 1 computer program, which implements several approximation concepts. A substantial collection of structural design problems involving truss and idealized wing structures is presented. It is concluded that since the basic ideas employed in creating the ACCESS 1 program are rather general, its successful development supports the contention that the introduction of approximation concepts will lead to the emergence of a new generation of practical and efficient, large scale, structural synthesis capabilities in which finite element analysis methods and mathematical programming algorithms will play a central role.

  13. The magnesium-ene cyclization stereochemically directed by an allylic oxyanionic group and its application to a highly stereoselective synthesis of (+/-)-matatabiether. Allylmagnesium compounds by reductive magnesiation of allyl phenyl sulfides.

    PubMed

    Cheng, D; Zhu, S; Yu, Z; Cohen, T

    2001-01-10

    The first example of a magnesium-ene cyclization stereochemically directed by an allylic oxyanionic group is demonstrated by a highly stereoselective synthesis of the bicyclic terpene matatabiether 10. The synthetic method is particularly valuable, not only because of the stereochemical control and the utility of the versatile hydroxyl group introduced into the product, but also because the precursor of the allylmagnesium is an allyl phenyl sulfide, which is more stable and more easily prepared in a connective fashion than the usual allyl halide precursor. Since the presence of lithium ions encourages undesirable proton transfer to the cyclized organometallic and is detrimental to the stereochemical control, the conversion of the allylic thioether to the allylmagnesium utilizes a lithium-free method involving direct reductive magnesiation in the presence of the magnesium-anthracene complex.

  14. Stereoselectively fluorinated N-heterocycles: a brief survey.

    PubMed

    Hu, Xiang-Guo; Hunter, Luke

    2013-11-29

    The stereoselective incorporation of fluorine atoms into N-heterocycles can lead to dramatic changes in the molecules' physical and chemical properties. These changes can be rationally exploited for the benefit of diverse fields such as medicinal chemistry and organocatalysis. This brief review will examine some of the effects that fluorine substitution can have in N-heterocycles, including changes to the molecules' stability, their conformational behaviour, their hydrogen bonding ability, and their basicity. Finally, some methods for the synthesis of stereoselectively fluorinated N-heterocycles will also be reviewed.

  15. A highly stereoselective and flexible strategy for the convergent synthesis of long-chain polydeoxypropionates: application towards the synthesis of the glycolipid membrane components hydroxyphthioceranic and phthioceranic acid.

    PubMed

    Pischl, Matthias C; Weise, Christian F; Haseloff, Stefan; Müller, Marc-André; Pfaltz, Andreas; Schneider, Christoph

    2014-12-22

    A highly stereocontrolled and flexible access to biologically relevant polydeoxypropionates in optically pure form has been developed. Taking advantage of our previously established strategy for the asymmetric and stereodivergent synthesis of trideoxypropionate building blocks, we have now been able to assemble large polydeoxypropionate chains with defined configuration in a highly convergent manner. Central steps of this approach include two Suzuki-Miyaura cross-coupling reactions with subsequent highly diastereoselective hydrogenations to join three advanced synthetic intermediates in excellent yield and with full stereochemical control. We have applied this strategy successfully towards the asymmetric synthesis of glycolipid membrane components phthioceranic acid and hydroxyphthioceranic acid, the latter of which was synthesized on a half-gram scale.

  16. Stereoselective Synthesis of Spiro Bis-C,C-α-arylglycosides by Tandem Heck Type C-Glycosylation and Friedel-Crafts Cyclization.

    PubMed

    Chen, Yen-Bo; Liu, Shi-Hao; Hsieh, Min-Tsang; Chang, Chih-Shiang; Lin, Chun-Hung; Chen, Chen-Yin; Chen, Po-Yen; Lin, Hui-Chang

    2016-04-01

    Spiro bis-C,C-α-arylglycosides were synthesized in three steps in 78-85% overall yields starting from exo-glycals. The initial Heck type C-aryl addition of exo-glycals with arylboronic acids afforded α-aryl-β-substituted C-glycosides with exclusive α-stereoselectivity. Among the products, β-ethanal α-aryl C-glycosides further reacted with alkylthiol in the presence of InCl3, followed by in situ Friedel-Crafts cyclization to yield the desirable final products. We proposed a mechanism to explain how the α-aryl group serves as a main determinant of the cyclization.

  17. Efficient synthesis of benzamide riboside, a potential anticancer agent.

    PubMed

    Bonnac, Laurent F; Gao, Guang-Yao; Chen, Liqiang; Patterson, Steven E; Jayaram, Hiremagalur N; Pankiewicz, Krzysztof W

    2007-01-01

    An efficient five step synthesis of benzamide riboside (BR) amenable for a large scale synthesis has been developed. It allows for extensive pre-clinical studies of BR as a potential anticancer agent.

  18. Stereoselective synthesis of 2-C-branched (acetylmethyl) oligosaccharides and glycoconjugates: Lewis acid-catalyzed glycosylation from 1,2-cyclopropaneacetylated sugars.

    PubMed

    Tian, Qiang; Dong, Liang; Ma, Xiaofeng; Xu, Liyan; Hu, Changwei; Zou, Wei; Shao, Huawu

    2011-02-18

    1,2-Cyclopropaneacetylated sugars as glycosyl donors reacted with a series of glycosyl acceptors (monosaccharides, amino acids, and other alcohols) in the presence of Lewis acid to produce oligosaccharides and glycoconjugates containing 2-C-acetylmethylsugars. Galactosyl donor gave good to excellent α-selectivities with TMSOTf as a catalyst, whereas galactosyl donor offered moderate to good β-selectivities when BF(3)·Et(2)O was used as a catalyst. However, glucosyl donors produced β-exclusive selectivity under both conditions. The stereoselectivities of glycosylation depend on the reactivity of donor sugars and Lewis acid catalyst, which effectively dictated the glycosylation pathways. The evidence suggests that galactosyl donors (e.g., 7) can undergo S(N)1 pathway with a strong Lewis acid (TMSOTf) and S(N)2 pathway under BF(3)·Et(2)O, whereas the glucosyl donors (e.g., 8 and 10) followed S(N)2 pathway. The stereoselectivity was also consequential to the formation of a C2'-acetal intermediate formed via the 2-C-acetylmethyl group and the anomeric carbonium intermediate in glycosylation.

  19. Efficient synthesis of phosphatidylserine in 2-methyltetrahydrofuran.

    PubMed

    Duan, Zhang-Qun; Hu, Fei

    2013-01-10

    2-Methyltetrahydrofuran has recently been described as a promising and green solvent. Herein, it was successfully used as the reaction medium for enzyme-mediated transphosphatidylation of phosphatidylcholine with L-serine with the aim of phosphatidylserine synthesis for the first time. Our results indicated that as high as 90% yield of phosphatidylserine could be achieved after 12 h combined with no byproduct (phosphatidic acid) forming. The present work accommodated a facilely and efficiently enzymatic strategy for preparing phosphatidylserine, which possessed obvious advantages over the reported processes in terms of high efficiency and environmental friendliness. This work is also a proof-of-concept opening the use of 2-methyltetrahydrofuran in biosynthesis as well.

  20. Regio- and stereoselective synthesis of pregnane-fused isoxazolines by nitril-oxide/alkene 1,3-dipolar cycloaddition and an evaluation of their cell-growth inhibitory effect in vitro

    NASA Astrophysics Data System (ADS)

    Mótyán, Gergő; Baji, Ádám; Zupkó, István; Frank, Éva

    2016-04-01

    Efficient syntheses of some pregnane-fused isoxazolines from 16-dehydropregnenolone acetate with different arylnitrile oxides were carried out by 1,3-dipolar cycloadditions. The intermolecular ring-closures occurred in a highly regio- and stereoselective manner permitting the formation of a single 16α,17α-condensed diastereomer in which the O terminus of the nitrile oxide dipole is attached to C-17 of the sterane core. The conversions were found to be affected significantly by the electronic character of the substituents on the aromatic moiety of the 1,3-dipoles. Deacetylation of the primary products resulted in the corresponding 3β-OH analogs. All of the synthesized compounds were subjected to in vitro pharmacological studies for the determination of their antiproliferative effects on four breast cancer cell lines (MCF7, T47D, MDA-MB-231 and MDA-MB-361).

  1. Azomethine Ylides from Nitrones: Using Catalytic nBuLi for the Totally Stereoselective Synthesis of trans-2-Alkyl-3-oxazolines.

    PubMed

    Juste-Navarro, Veronica; Delso, Ignacio; Tejero, Tomás; Merino, Pedro

    2016-08-08

    The cycloaddition of azomethine ylide N-oxides (nitrone ylides) with aldehydes provides 3-oxazolines in a completely stereoselective manner in the presence of a catalytic amount of n-butyllithium. The process involves an initial nucleophilic attack on the aldehyde, followed by intramolecular oxygen addition to the nitrone moiety and lithium-assisted elimination of water, regenerating the catalytic species. Various Li-based catalytic systems are possible and the in situ generated water is required for continuing the catalytic cycle. The best results are observed with 20 mol % of n-butyllithium, whereas the use of stoichiometric amounts inhibit the rate of catalysis. Experimental, spectroscopic, and computational mechanistic studies have provided evidence of lithium-ion catalysis and rationalized several competing catalytic pathways.

  2. New chiral phosphinephosphinite ligands: Application to stereoselective synthesis of a key intermediate of 1{beta}-methyl carbapenems by Rh(I)-catalyzed asymmetric hydroformylation

    SciTech Connect

    Saito, Takao; Yoshida, Akifumi; Matsumura, Kazuhiko

    1995-12-31

    Transition metal catalyzed asymmetric hydroformylation is an attractive and highly useful homologation process for organic synthesis. Recently, the authors reported that the Rh(I) complexes of phosphinephosphite BINAPHOS are highly efficient catalysts for enantioselective hydroformylation of a variety of olefins. This time, the authors have designed and synthesized new chiral phosphinephosphinite ligands having binaphthyl backbone, (R)-2-diarylphosphino-2{prime}-diarylphosphinoxy-1,1{prime}-binaphthy1 (hereafter abbreviated (R)-BIPNITE). The Rh(I) complexes of these ligands are effective catalysts for the asymmetric hydroformylation of 4-vinylazetidin-2-one to give the corresponding oxo-aldehyde 3{beta} as the major product in very high diastereoselectivities and in good regioselectivities. Interestingly, modifications of the aryl substituents in phosphine and phosphinite moieties afforded higher selectivities. Aldehyde 3{beta} was easily oxidized with NaClO{sub 2} to 4, a key intermediate of 1{beta}-methyl carbapenems. Thus, the present method provides a new practical route to a versatile key intermediate for the synthesis of carbapenem antibiotics.

  3. Regio- and Stereoselective Modification of Chiral α-Amino Ketones by Pd-Catalyzed Allylic Alkylation.

    PubMed

    Huwig, Kai; Schultz, Katharina; Kazmaier, Uli

    2015-07-27

    Chiral α-amino ketones are excellent nucleophiles for stereoselective palladium-catalyzed allylic alkylations. Both chiral as well as achiral allylic substrates can be applied, while the stereochemical outcome of the reaction is controlled by the chiral ketone enolate. The substituted amino ketones formed can be reduced stereoselectively, and up to five consecutive stereogenic centers can be obtained. This approach can be used for the synthesis of highly substituted piperidine derivatives.

  4. Enzymatic resolution of racemates with a 'remote' stereogenic center as an efficient tool in drug, flavor and vitamin synthesis.

    PubMed

    Alfaro Blasco, Maria; Gröger, Harald

    2014-10-15

    The enantioselective recognition of 'remote' stereogenic centers represents a scientific task in organic chemistry being also of current interest in the pharmaceutical industry. This is due to a range of pharmaceutically relevant molecules or intermediates thereof bearing a stereogenic center, which is separated from the functional group by a larger non-chiral moiety such as, for example, a longer sequence of bonds of at least three carbon or hetero-atoms or by a planar aromatic moiety. Notably, biocatalysis turned out to provide an excellent solution for a range of challenging syntheses in this field. For example, efficient enzymatic resolution processes of racemates with such a 'remote' stereogenic center were developed for the synthesis of pelitrexol, lasofoxifene and (S)-monastrol. In general, good yields accompanied by high enantioselectivities were obtained, thus underlining the tremendous potential of enzymes to recognize and enantioselectively transform enantiomers of racemates with 'remote' stereogenic centers. Such or similar types of stereoselective recognitions of 'remote' stereogenic centers by means of enzymes have been also reported in the field of flavor and vitamin synthesis. Thus, biocatalysis represents a promising solution for the efficient approach to enantiomerically pure complex chiral molecules with stereogenic centers being located apart from the functional group, and it can be expected that enzymatic resolution will be increasingly applied when searching for an efficient and also technically feasible process for also novel complex chiral molecules bearing a 'remote' stereogenic center.

  5. Synthesis of cyclic sulfones by ring-closing metathesis.

    PubMed

    Yao, Qingwei

    2002-02-07

    A general and highly efficient synthesis of cyclic sulfones based on ring-closing metathesis has been developed. The synthetic utility of the resulting cyclic sulfones was demonstrated by their participation in stereoselective Diels-Alder reactions and transformation to cyclic dienes by the Ramberg-Bäcklund reaction.

  6. Total synthesis of (±)-maistemonine and (±)-stemonamide.

    PubMed

    Chen, Zhi-Hua; Zhang, Yong-Qiang; Chen, Zhi-Min; Tu, Yong-Qiang; Zhang, Fu-Min

    2011-02-14

    The first total synthesis of polycyclic Stemona alkaloid maistemonine has been achieved. The efficient approach features a stereoselective intramolecular Schmidt reaction, a ketone-ester condensation, and a Reformatsky reaction. Additionally, another Stemona alkaloid stemonamide was divergently synthesized from a common intermediate.

  7. Stereoselective Glycosylation of 2-Nitrogalactals Catalyzed by a Bifunctional Organocatalyst

    PubMed Central

    2016-01-01

    The use of a bifunctional cinchona/thiourea organocatalyst for the direct and α-stereoselective glycosylation of 2-nitrogalactals is demonstrated for the first time. The conditions are mild, practical, and applicable to a wide range of glycoside acceptors with products being isolated in good to excellent yields. The method is exemplified in the synthesis of mucin type Core 6 and 7 glycopeptides. PMID:27529800

  8. Regiodivergent and Stereoselective Hydrosilylation of 1,3-Disubstituted Allenes.

    PubMed

    Miller, Zachary D; Dorel, Ruth; Montgomery, John

    2015-07-27

    Methods for the highly stereoselective and regiodivergent hydrosilylation of 1,3-disubstituted allenes have been developed. The synthesis of E allylsilanes is accomplished with palladium NHC catalysts, and trisubstituted Z alkenylsilanes are accessed with nickel NHC catalysts. Unsymmetrically substituted allenes are well tolerated with nickel catalysis and afford Z alkenylsilanes. Evidence for a plausible mechanism was obtained through an isotopic double-labeling crossover study.

  9. Chemoenzymatic collective synthesis of optically active hydroxyl(methyl)tetrahydronaphthalene-based bioactive terpenoids.

    PubMed

    Batwal, Ramesh U; Argade, Narshinha P

    2015-12-14

    Starting from succinic anhydride and 2-methylanisole, a chemoenzymatic collective formal/total synthesis of several optically active tetrahydronaphthalene based bioactive natural products has been presented via advanced level common precursors; the natural product and antipode (-)/(+)-aristelegone B. Regioselective benzylic oxidations, stereoselective introduction of hydroxyl groups at the α-position of ketone moiety in syn-orientation, efficient enzymatic resolutions with high enantiomeric purity, stereoselective reductions, samarium iodide induced deoxygenations and tandem acylation-Wittig reactions without racemization and/or eliminative aromatization were the key features. An attempted diastereoselective synthesis of (±)-vallapin has also been described.

  10. An efficient chemical synthesis of nicotinamide riboside (NAR) and analogues.

    PubMed

    Tanimori, Shinji; Ohta, Takeshi; Kirihata, Mitsunori

    2002-04-22

    A simple and efficient synthesis of nicotinamide riboside (NAR) 1 and derivatives 4 and 5 via trimethylsilyl trifluoromethanesulfonate (TMSOTf)-mediated N-glycosilation followed by spontaneous deacetylation by treating with methanol is reported.

  11. Short and efficient synthesis of fluorinated δ-lactams.

    PubMed

    Cogswell, Thomas J; Donald, Craig S; Long, De-Liang; Marquez, Rodolfo

    2015-01-21

    The diastereoselective synthesis of fluorinated δ-lactams has been achieved through an efficient five step process. The route can tolerate a range of functionalities, and provides a quick route for the generation of new fluorinated medicinal building blocks.

  12. Protecting groups in carbohydrate chemistry: influence on stereoselectivity of glycosylations.

    PubMed

    Guo, Jian; Ye, Xin-Shan

    2010-10-20

    Saccharides are polyhydroxy compounds, and their synthesis requires complex protecting group manipulations. Protecting groups are usually used to temporarily mask a functional group which may interfere with a certain reaction, but protecting groups in carbohydrate chemistry do more than protecting groups usually do. Particularly, protecting groups can participate in reactions directly or indirectly, thus affecting the stereochemical outcomes, which is important for synthesis of oligosaccharides. Herein we present an overview of recent advances in protecting groups influencing stereoselectivity in glycosylation reactions, including participating protecting groups, and conformation-constraining protecting groups in general.

  13. Highly Stereoselective Synthesis of Anti, Anti-Dipropionate Stereotriads: A Solution to the Long-Standing Problem of Challenging Mismatched Double Asymmetric Crotylboration Reactions#

    PubMed Central

    Chen, Ming; Roush, William R.

    2012-01-01

    The stereocontrolled synthesis of the β-branched anti, anti-dipropionate stereotriad 4 via aldol or crotylmetal chemistry represents a historical challenge to the organic synthesis community. Here we describe a general solution to the long-standing problem associated with the synthesis of 4 by utilizing mismatched double asymmetric crotylboration reactions of enantioenriched α-methyl substituted aldehydes with the chiral, nonracemic crotylborane reagent (S)-(E)-22 (or its enantiomer). This method not only provides direct access to anti, anti-dipropionate stereotriads 24 [a synthetic equivalent of 4] with very good (5-8:1) if not excellent (≥15:1) diastereoselectivity from β-branched chiral aldehydes with ≤50:1 intrinsic diastereofacial selectivity preferences, but also provides a vinylstannane unit in the products that is properly functionalized for use in subsequent C-C bond forming events. We anticipate that this method will be widely applicable and will lead to substantial simplification of strategies for synthesis of polyketide natural products. PMID:22332989

  14. Total Synthesis of Mycolactones A and B

    PubMed Central

    Song, Fengbin; Fidanze, Steve; Benowitz, Andrew B.; Kishi, Yoshito

    2007-01-01

    First and second generation total syntheses of mycolactones A and B are reported. The first generation total synthesis unambiguously confirmed our earlier assignment of the relative and absolute stereochemistry of mycolactones A and B. Knowledge of the chemical properties of the mycolactones accumulated through the first generation total synthesis allowed us to implement several major improvements to the original synthesis, including: (1) optimizing the choice of protecting groups, (2) eliminating the unnecessary adjustment of protecting groups, and (3) improving the overall stereoselectivity and synthetic efficiency. The second generation total synthesis consists of 21 longest linear steps, with 8.8% overall yield. PMID:17940589

  15. Efficient preparation of terminal conjugated dienes by coupling of dienol phosphates with grignard reagents under iron catalysis.

    PubMed

    Cahiez, Gérard; Habiak, Vanessa; Gager, Olivier

    2008-06-19

    An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.

  16. An Efficient Microscale Procedure for the Synthesis of Aspirin

    NASA Astrophysics Data System (ADS)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

    The synthesis of aspirin is a part of many undergraduate organic synthesis labs and is frequently used in qualitative organic analysis laboratory for the identification of salicylic acid. We have found that aspirin can be synthesized on microscale by a simple and efficient procedure that eliminates the heating step employed in literature procedures and gives a pure, ferric-negative product (no purple color with alcoholic ferric chloride solution).

  17. Hydroxyl-directed stereoselective diboration of alkenes.

    PubMed

    Blaisdell, Thomas P; Caya, Thomas C; Zhang, Liang; Sanz-Marco, Amparo; Morken, James P

    2014-07-02

    An alkoxide-catalyzed directed diboration of alkenyl alcohols is described. This reaction occurs in a stereoselective fashion and is demonstrated with cyclic and acyclic homoallylic and bishomoallylic alcohol substrates. After oxidation, the reaction generates 1,2-diols such that the process represents a method for the stereoselective directed dihydroxylation of alkenes.

  18. Practical asymmetric synthesis of a potent PDE4 inhibitor via stereoselective enolate alkylation of a chiral aryl-heteroaryl secondary tosylate.

    PubMed

    O'Shea, Paul D; Chen, Cheng-yi; Chen, Weirong; Dagneau, Philippe; Frey, Lisa F; Grabowski, Edward J J; Marcantonio, Karen M; Reamer, Robert A; Tan, Lushi; Tillyer, Richard D; Roy, Amélie; Wang, Xin; Zhao, Dalian

    2005-04-15

    A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to 1 was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield.

  19. New uses for the Burgess reagent in chemical synthesis: methods for the facile and stereoselective formation of sulfamidates, glycosylamines, and sulfamides.

    PubMed

    Nicolaou, K C; Snyder, Scott A; Longbottom, Deborah A; Nalbandian, Annie Z; Huang, Xianhai

    2004-11-05

    Although the Burgess reagent (methoxycarbonylsulfamoyltriethylammonium hydroxide, inner salt) has found significant use in chemical synthesis as a dehydrating agent, almost no work has been directed towards its potential in other synthetic applications. As this article will detail, we have found that the Burgess reagent is remarkably effective at accomplishing a number of non-dehydrative synthetic tasks when applied to appropriate substrates, such as the formation of sulfamidates from 1,2-diols or epoxyalcohols, alpha- and beta-glycosylamines from carbohydrates, and cyclic sulfamides from 1,2-aminoalcohols. Beyond delineating the power of these new reaction manifolds, we also describe the construction of a group of alternative Burgess-type reagents that extends the scope of these new reactions even further.

  20. Regio‐ and Stereoselective Homologation of 1,2‐Bis(Boronic Esters): Stereocontrolled Synthesis of 1,3‐Diols and Sch 725674

    PubMed Central

    Fawcett, Alexander; Nitsch, Dominik; Ali, Muhammad; Bateman, Joseph M.; Myers, Eddie L.

    2016-01-01

    Abstract 1,2‐Bis(boronic esters), derived from the enantioselective diboration of terminal alkenes, can be selectively homologated at the primary boronic ester by using enantioenriched primary/secondary lithiated carbamates or benzoates to give 1,3‐bis(boronic esters), which can be subsequently oxidized to the corresponding secondary‐secondary and secondary‐tertiary 1,3‐diols with full stereocontrol. The transformation was applied to a concise total synthesis of the 14‐membered macrolactone, Sch 725674. The nine‐step synthetic route also features a novel desymmetrizing enantioselective diboration of a divinyl carbinol derivative and high‐yielding late‐stage cross‐metathesis and Yamaguchi macrolactonization reactions. PMID:27781356

  1. Photophysics of a new photosensitizer with high quantum yield of singlet oxygen generation and its application to stereo-selective synthesis of (+)-deoxoartemisinin

    NASA Astrophysics Data System (ADS)

    Wang, Kang-Kyun; Choi, Kyoung-Hoon; Shin, Hee-Won; Kim, Bong-Jin; Im, Ji-Eun; Oh, Seung-Lim; Park, Nam-Soo; Jung, Mankil; Oh, Jae-Buem; Lee, Myung-Jun; Kim, Hwan-Kyu; Kim, Yong-Rok

    2009-11-01

    A new photo-catalyst of [5,10,15-triphenyl-20-(4-methoxycarbonylphenyl)-porphyrin] platinum was synthesized and its photophysical study revealed that it had a high quantum yield of singlet oxygen generation. As an application study, a stereo-specific synthesis of (+)-deoxoartemisinin was performed. The induced high triplet quantum yield (0.96 ± 0.03) of [5,10,15-triphenyl-20-(4-methoxycarbonylphenyl)-porphyrin] resulted the high singlet oxygen quantum yield of 0.90 ± 0.04. The photo-catalytic effect was compared with that of methylene blue (MB) which was generally used as a photo-catalyst for these types of stereo-specific syntheses of organic compounds. The yield of synthesized (+)-deoxoartemisinin was correlated with singlet oxygen quantum yield.

  2. Rapid and Stereoselective Conversion of a "trans"-Cinnamic Acid to a beta-Bromostyrene

    ERIC Educational Resources Information Center

    Evans, Thomas A.

    2006-01-01

    The stereoselective synthesis of an aryl vinyl bromide is accomplished in a rapid microscale reaction of "trans"-4-methoxycinnamic acid with N-bromosuccinimide in dichloromethane. The product is purified by dry column vacuum chromatography and its stereochemistry is determined by [superscript 1]H NMR. TLC, GC and GC-MSD can also be used. This…

  3. Types of stereoselectivity in drug metabolism: a heuristic approach.

    PubMed

    Testa, Bernard

    2015-05-01

    Stereochemical factors are known to play a significant role in the metabolism of drugs and other xenobiotics. Following Prelog's lead, types of metabolic stereoselectivity can be categorized as (i) substrate stereoselectivity (the differential metabolism of two or more stereoisomeric substrates) and (ii) product stereoselectivity (the differential formation of two or more stereoisomeric metabolites from a single substrate). Combinations of the two categories exist as (iii) substrate-product stereoselectivities, meaning that product stereoselectivity itself is substrate stereoselective. Here, published examples of metabolic stereoselectivities are examined in the light of these concepts. In parallel, a graphical scheme is presented with a view to facilitate learning and help researchers to solve classification problems.

  4. Palladium-catalyzed stereoselective intramolecular oxidative amidation of alkenes in the synthesis of 1,3- and 1,4-amino alcohols and 1,3-diamines.

    PubMed

    Malkov, Andrei V; Lee, Darren S; Barłóg, Maciej; Elsegood, Mark R J; Kočovský, Pavel

    2014-04-22

    An efficient and practical Pd-catalyzed intramolecular oxidative allylic amidation provides facile access to derivatives of 1,3- and 1,4-amino alcohols and 1,3-diamines. The method operates under mild reaction conditions (RT) with molecular oxygen (1 atm) as the sole reoxidant of Pd. Excellent diastereoselectivities were attained with substrates bearing a secondary stereogenic center.

  5. A stereoselective approach to peptidomimetic BACE1 inhibitors.

    PubMed

    Butini, Stefania; Gabellieri, Emanuele; Brindisi, Margherita; Giovani, Simone; Maramai, Samuele; Kshirsagar, Giridhar; Guarino, Egeria; Brogi, Simone; La Pietra, Valeria; Giustiniano, Mariateresa; Marinelli, Luciana; Novellino, Ettore; Campiani, Giuseppe; Cappelli, Andrea; Gemma, Sandra

    2013-01-01

    Aiming at identifying new scaffolds to generate beta-secretase (BACE1) inhibitors we developed peptidomimetics based on a 1,4-benzodiazepine core (3a-d), their seco-analogs (4a-b), and linear analogs (5a-h), by stereoselective approaches. We herein discuss the synthesis, molecular modeling and in vitro studies for the newly developed ligands. Compounds 5c and 5h behaved as BACE1 inhibitors on the isolated enzyme and in cellular studies. Particularly, for its low molecular weight, inhibitor 5h is a prototypic hit to develop a series of BACE1 inhibitors more potent and active on whole-cells.

  6. Facile and efficient synthesis of isolongifolenone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An efficient method for preparation of isolongifolenone by oxidation of isolongifolene in high yield with a short reaction time is described. Highly allylic oxidation selectivity was achieved by using tert-butyl hydroperoxide as the oxidant and chromium hexacarbonyl as the catalyst. The oxidative ...

  7. Efficient asymmetric synthesis of [7]helicene bisquinones.

    PubMed

    Carreño, M Carmen; González-López, Marcos; Urbano, Antonio

    2005-02-07

    The efficient one-pot six-step domino process which occurs when (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1) reacts with 3,6-divinyl-1,2,7,8-tetrahydrophenanthrenes 2a-c allowed enantioselective access to [7]helicene bisquinones 3a-c with excellent optical purities (96 to > 99% ee).

  8. Magnesium-mediated intramolecular reductive coupling: a stereoselective synthesis of C(2)-symmetric 3,4-bis-silyl-substituted adipic acid derivatives.

    PubMed

    Kundu, Pintu K; Ghosh, Sunil K

    2009-11-21

    Chiral C(2)-symmetric 3,4-bis-silyl-substituted adipic acid derivatives have been synthesised by a Mg/trimethylsilyl chloride-mediated intramolecular reductive coupling of symmetrical disiloxanes of beta-silylacrylic acid N-oxazolidinone derivatives. Efficient and short syntheses of enantiomerically pure enantiomers of 2,6-dioxabicyclo[3.3.0]octane-3,7-dione have been achieved from the bis-silylated adipic acid derivatives using Fleming-Tamao oxidation as the key step.

  9. Configuration Synthesis and Efficient Motion Programming of Robot Manipulators

    DTIC Science & Technology

    1991-03-15

    Efficient Motion Programming of Robot Manipulators P og DAAL 03-87-K-0041 6. AUTHOR(S) K.C. Gupta 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) B...this research was to study the factors which influ- ence the design of robot arms and wrists (configuration synthesis). Another objective was to...develop efficient computational software tools for the manipulation of industrial robots . These software tools were to address the critical problems which

  10. Efficient and selective synthesis of D-arabino-, D-lyxo-, and D-xylo-phytosphingosine from D-ribo-phytosphingosine.

    PubMed

    Kim, Sanghee; Lee, Nakyong; Lee, Sukjin; Lee, Taeho; Lee, Yun Mi

    2008-02-15

    A new high-yield approach to the regio- and stereoselective synthesis of d-arabino-, D-lyxo-, and D-xylo-phytosphingosines from inexpensive D-ribo-phytosphingosine is described. The synthetic methodologies mainly rely on the selective configurational inversion of the stereocenter through a neighboring group participation mechanism.

  11. Efficient view synthesis from uncalibrated stereo

    NASA Astrophysics Data System (ADS)

    Braspenning, Ralph; Op de Beeck, Marc

    2006-02-01

    For multiview auto-stereoscopic 3D displays, available stereo content needs to be converted to multiview content. In this paper we present a method to efficiently synthesize new views based on the two existing views from the stereo input. This method can be implemented in real-time and is also capable of handling uncalibrated stereo input. Good performance is shown compared to state-of-the-art disparity estimation algorithms and view rendering methods.

  12. Stereoselective microbial dehalorespiration with vicinal dichlorinated alkanes.

    PubMed

    De Wildeman, Stefaan; Diekert, Gabriele; Van Langenhove, Herman; Verstraete, Willy

    2003-09-01

    The suspected carcinogen 1,2-dichloroethane (1,2-DCA) is the most abundant chlorinated C(2) groundwater pollutant on earth. However, a reductive in situ detoxification technology for this compound does not exist. Although anaerobic dehalorespiring bacteria are known to catalyze several dechlorination steps in the reductive-degradation pathway of chlorinated ethenes and ethanes, no appropriate isolates that selectively and metabolically convert them into completely dechlorinated end products in defined growth media have been reported. Here we report on the isolation of Desulfitobacterium dichloroeliminans strain DCA1, a nutritionally defined anaerobic dehalorespiring bacterium that selectively converts 1,2-dichloroethane and all possible vicinal dichloropropanes and -butanes into completely dechlorinated end products. Menaquinone was identified as an essential cofactor for growth of strain DCA1 in pure culture. Strain DCA1 converts chiral chlorosubstrates, revealing the presence of a stereoselective dehalogenase that exclusively catalyzes an energy-conserving anti mechanistic dichloroelimination. Unlike any known dehalorespiring isolate, strain DCA1 does not carry out reductive hydrogenolysis reactions but rather exclusively dichloroeliminates its substrates. This unique dehalorespiratory biochemistry has shown promising application possibilities for bioremediation purposes and fine-chemical synthesis.

  13. Facile synthesis of fluoroalkenes by palladium-catalyzed reductive defluorination of allylic gem-difluorides.

    PubMed

    Narumi, Tetsuo; Tomita, Kenji; Inokuchi, Eriko; Kobayashi, Kazuya; Oishi, Shinya; Ohno, Hiroaki; Fujii, Nobutaka

    2007-08-16

    Chemo- and stereoselective synthesis of fluoroalkenes was achieved in excellent yields via Pd-catalyzed C-F bond activation. In this transformation, Et3N plays a crucial role to produce reactive hydride species such as Ph(EtO)SiH2 and Ph(EtO)2SiH by promoting dehydrogenative coupling. The reaction proceeds efficiently at 50 degrees C with a variety of substrates and is also useful for the synthesis of fluoroalkene peptidomimetics.

  14. Total synthesis of a new cytotoxic acetogenin, jimenezin, and the revised structure.

    PubMed

    Takahashi, S; Maeda, K; Hirota, S; Nakata, T

    1999-12-16

    The first total synthesis of jimenezin was achieved by using carbohydrates as chiral building blocks, thus revising the proposed structure 1 to 2. The key steps in this synthesis include an efficient construction of the THP-THF fragments 3 and 16 through a stereoselective condensation between the pyranyl aldehyde 5 and the acetylene derivative 6, and a palladium-catalyzed coupling reaction of 3 or 16 with a terminal butenolide 4.

  15. Efficient synthesis of eudistomin U and evaluation of its cytotoxicity.

    PubMed

    Roggero, Chad M; Giulietti, Jennifer M; Mulcahy, Seann P

    2014-08-01

    Eudistomin U is a member of a subclass of naturally occurring indole alkaloids known as β-carbolines. These molecules are reported to have diverse biological activity and high binding affinity to DNA, which make them attractive targets for total synthesis. We describe an efficient, five-step synthesis of eudistomin U by employing two key reactions: a Bischler-Napieralski cyclization and a Suzuki cross coupling. We also describe the cytotoxicity of eudistomin U against various cancer cell lines and human pathogens, in which we observed potent antibacterial activity against Gram-positive bacteria.

  16. Stereocontrolled total synthesis of (+)-vincristine

    PubMed Central

    Kuboyama, Takeshi; Yokoshima, Satoshi; Tokuyama, Hidetoshi; Fukuyama, Tohru

    2004-01-01

    An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine presursor. Demethylvindoline was prepared by oxidation of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindoline formamide was not successful and resulted in recovery of the starting compounds, the reaction using demethylvindoline took place smoothly to furnish the desired bisindole product with the correct stereochemistry at C18′. After formation of the piperidine ring by sequential removal of the protective groups and intramolecular nucleophilic cyclization, the total synthesis of vincristine was completed by formylation of N1. PMID:15141084

  17. Selenide-Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes.

    PubMed

    Wu, Jin-Ji; Xu, Jia; Zhao, Xiaodan

    2016-10-17

    The efficient regio- and stereoselective construction of tetrasubstituted alkenes is challenging and very important. For this purpose, we have developed an efficient approach to synthesize tetrasubstituted trifluoromethylthiolated alkenes from simple alkynes in excellent regio- and stereoselectivities by selenide-catalyzed multicomponent coupling. Using this method, trifluoromethylthiolated alkenyl triflates and arenes were achieved. In particular, the triflates could be further converted into carbofunctionalized alkenes by palladium-catalyzed cross-coupling reactions. Our method provides a new pathway for the construction of trifluoromethylthiolated tricarboalkenes. This work presents the first example of selenide-catalyzed trifluoromethylthiolation of alkynes and enables the challenging functionalizations of alkynes.

  18. An efficient and sustainable synthesis of NHC gold complexes.

    PubMed

    Johnson, Alice; Gimeno, M Concepción

    2016-08-11

    A simple, efficient and sustainable method for the general synthesis of NHC gold(i) complexes is described. The reaction of imidazolium salts, of different electronic and steric requirements, with [AuX(tht)] (tht = tetrahydrothiophene) derivatives, in the presence of NBu4(acac), in air and at room temperature leads to the NHC gold species in good yields and with very short reaction times.

  19. Efficient chemoenzymatic synthesis of sialyl Tn-antigen and derivatives†

    PubMed Central

    Ding, Li; Yu, Hai; Lau, Kam; Li, Yanhong; Muthana, Saddam; Wang, Junru; Chen, Xi

    2011-01-01

    An N-terminal and C-terminal truncated recombinant α2–6-sialyltransferase cloned from Photobacterium sp. JH-ISH-224, Psp2,6ST(15–501)-His6, was shown to be an efficient catalyst for one-pot three-enzyme synthesis of sialyl Tn (STn) antigens and derivatives containing natural and non-natural sialic acid forms. PMID:21725542

  20. Stereoselective synthesis of (+)-euphococcinine and (-)-adaline.

    PubMed

    Arbour, Mélissa; Roy, Stéphanie; Godbout, Cédrickx; Spino, Claude

    2009-05-15

    We describe the syntheses of (+)-euphococcinine and (-)-adaline, two naturally occurring alkaloids containing a quaternary carbon bearing a nitrogen atom. Key features of the syntheses are a 3,3-sigmatropic rearrangement to give an all-carbon quaternary center, a ring-closing alkene metathesis to give an 8-membered ring, and the use of a single enantiomer of p-menthane-3-carboxaldehyde to make two natural alkaloids of opposite configuration.

  1. Solid-Phase Synthesis of ɤ-Lactone and 1,2-Oxazine Derivatives and Their Efficient Chiral Analysis

    PubMed Central

    Krupkova, Sona; Aguete, Gonzalo Pazos; Kocmanova, Leona; Volna, Tereza; Grepl, Martin; Novakova, Lucie; Miller, Marvin John; Hlavac, Jan

    2016-01-01

    Derivatives of 3-methyl-3,6-dihydro-2H-1,2-oxazine-6-carboxylic acid prepared by regioselective hetero Diels-Alder reaction of arylnitroso compounds with sorbic acid were used for solid-phase synthesis of a library of derivatives that included modification of carboxylic group, dihydroxylation of double bond and cleavage of N-O bond. Derivatives of 2,3,4-trihydroxyhexanoic acid obtained from 3,6-dihydro-2H-1,2-oxazines after double bond dihydroxylation and N-O cleavage were used for simple and stereoselective formation of chiral lactones derived from 3,4-dihydroxydihydrofuran-2(3H)-one. The final compounds obtained as a mixture of stereoisomers were analyzed with use of chiral HPLC and SFC. HPLC analyses were not successful for all derivatives or required lengthy chromatography. On the other hand SFC afforded much shorter analyses and was effective for all studied derivatives. The method of synthesis and analysis is thus suitable for future study of stereoselective synthesis of lactones and other derivatives from single oxazine derivatives and application of high-throughput synthesis on solid-support and combinatorial chemistry. PMID:27893812

  2. Synthesis of a Precursor to Sacubitril Using Enabling Technologies.

    PubMed

    Lau, Shing-Hing; Bourne, Samuel L; Martin, Benjamin; Schenkel, Berthold; Penn, Gerhard; Ley, Steven V

    2015-11-06

    An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield.

  3. Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers.

    PubMed

    Seeman, P; Westman, K; Protiva, M; Jílek, J; Jain, P C; Saxena, A K; Anand, N; Humber, L; Philipp, A

    1979-06-15

    In order to identify a pair of neuroleptic enantiomers with the highest stereoselective interaction with neuroleptic/dopamine receptors, the effects of eight pairs of neuroleptic enantiomers were tested on the specific binding of 3H-spiperone to crude homogenates of calf caudate nucleus. The ratios of the Ki values were: (+)-butaclamol/(-)-butaclamol = 3000; dexclamol/(-)-analogue = 151; (+)-isobutaclamol/(-)-isobutaclamol = 146; (-)-CTC/(+)-CTC= 109; (-)-centbutindole/(+)-centbutindole = 20; S(+)-octoclothepin/R(-)-octoclothepin = 11. Thus, the neuroleptic receptor is highly stereoselective for the rigid butaclamol derivatives, but much less so for the flexible neuroleptics. The 3H-apomorphine binding site, however, had a stereoselectivity ratio of only 7 for isobutaclamol, further suggesting that the high affinity sites (i.e. nM) for 3H-neuroleptic binding and for 3H-apomorphine binding are different.

  4. Total Synthesis of (±)-Englerin A Using An Intermolecular [3+2] Cycloaddition Reaction of Platinum-Containing Carbonyl Ylide.

    PubMed

    Kusama, Hiroyuki; Tazawa, Aoi; Ishida, Kento; Iwasawa, Nobuharu

    2016-01-01

    Total synthesis of (±)-Englerin A has been achieved starting from γ,δ-ynone 5 in 14 steps. The key feature of this synthesis is the highly efficient and stereoselective preparation of 8-oxabicyclo[3.2.1]octane derivative 6, a core skeleton of Englerin A, based on an inverse electron-demand [3+2] cycloaddition reaction of the platinum-containing carbonyl ylide, which was developed in our laboratory.

  5. A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids

    PubMed Central

    Enoki, Junichi; Meisborn, Jaqueline; Müller, Ann-Christin; Kourist, Robert

    2016-01-01

    A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material. PMID:27092111

  6. A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids.

    PubMed

    Enoki, Junichi; Meisborn, Jaqueline; Müller, Ann-Christin; Kourist, Robert

    2016-01-01

    A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material.

  7. High Efficient Synthesis of Iron-based Superconductors

    NASA Astrophysics Data System (ADS)

    Fang, Ai-Hua; Huang, Fu-Qiang; Xie, Xiao-Ming; Jiang, Mian-Heng

    We have performed systematic investigations aimed at high efficient synthesis of the 1111 family iron-based superconductors. By using meta-stable reactive starting materials of LnAs and FeO, assisted by mechanical alloying and fast heating, high purity samples with Tconset greater than 50K can be made with sintering temperatures between 1433K-1073K, and sintering time from 20 min to 40 h. High purity phase with sintering temperature as low as 973K was demonstrated successfully although Tconset fall below 50K and weak grain boundary suppressed greatly the zero resistance temperature. Ultra fast microwave sintering brings the sintering time further down to 5 min. Samples prepared by the above high efficient methods typically posses submicron grain and very high upper critical field, indicating very high pinning power. Besides offering cost advantages, the developed methods may play important roles in the exploit of novel superconductors.

  8. Regio- and stereoselectivities in plant cell biotransformation

    SciTech Connect

    Hamada, H.

    1995-12-01

    The ability of plant cultured cells to convert foreign substrates into more useful substances is of considerable interest. Therefore I have studied biotransformation of foreign substrate by plant cell suspension cultures. In this presentation, I report regio- and stereoselectivities in biotransformation of steroids and indole alkaloids and taxol by plant (tobacco, periwinkle, moss, orchid) cell suspension cultures.

  9. Carbohydrates as enantioinduction components in stereoselective catalysis

    PubMed Central

    Henderson, Alexander S.

    2016-01-01

    Carbohydrate derivatives are readily available chiral molecules, yet they are infrequently employed as enantioinduction components in stereoselective catalysis. In this review, synthetic approaches to carbohydrate-based ligands and catalysts are outlined, along with example applications in enantioselective catalysis. A wide range of carbohydrate-based functionality is covered, and key trends and future opportunities are identified. PMID:27064817

  10. Efficient conversion of carbohydrates into 1-C-alditols: application to the synthesis of chiral gamma-substituted butenolides and bicyclic alkaloid analogues.

    PubMed

    Boto, Alicia; Hernández, Dácil; Hernández, Rosendo

    2008-07-18

    Readily available sugar derivatives were transformed in a few steps into valuable, more complex products. The tandem radical scission of carbohydrates-oxidation reaction gave acetoxy acetals, which were converted into a variety of chiral C-alditols in good global yields and excellent 1,2-trans stereoselectivity. The reaction was the key step in the synthesis of hydroxylated gamma-substituted butenolides and bicyclic alkaloid analogues.

  11. Controlled oxidation of remote sp3 C—H bonds in artemisinin via P450 catalysts with fine tuned regio and stereoselectivity

    PubMed Central

    Zhang, Kaidong; Shafer, Brian M.; Demars, Matthew D.; Stern, Harry A.; Fasan, Rudi

    2012-01-01

    The selective oxyfunctionalization of isolated sp3 C—H bonds in complex molecules represents a formidable challenge in organic chemistry. Here, we describe a rational, systematic strategy to expedite the development of P450 oxidation catalysts with refined regio and stereoselectivity for the hydroxylation of remote, unactivated C—H sites in a complex scaffold. Using artemisinin as model substrate, we demonstrate how a three tier strategy involving first sphere active site mutagenesis, high throughput P450 fingerprinting, and fingerprint driven P450 reactivity predictions enabled the rapid evolution of three efficient biocatalysts for the selective hydroxylation of a primary and a secondary C—H site (with both S and R stereoselectivity) in a relevant yet previously inaccessible region of this complex natural product. The evolved P450 variants could be applied to provide direct access to the desired hydroxylated derivatives at preparative scales (0.4 g) and in high isolated yields (>90%), thereby enabling further elaboration of this molecule. As an example, enantiopure C7 fluorinated derivatives of the clinical antimalarial drugs artesunate and artemether, in which a major metabolically sensitive site is protected by means of a C—H to C—F substitution, were afforded via P450 mediated chemoenzymatic synthesis. PMID:23121379

  12. Engineering the elongation factor Tu for efficient selenoprotein synthesis.

    PubMed

    Haruna, Ken-ichi; Alkazemi, Muhammad H; Liu, Yuchen; Söll, Dieter; Englert, Markus

    2014-09-01

    Selenocysteine (Sec) is naturally co-translationally incorporated into proteins by recoding the UGA opal codon with a specialized elongation factor (SelB in bacteria) and an RNA structural signal (SECIS element). We have recently developed a SECIS-free selenoprotein synthesis system that site-specifically--using the UAG amber codon--inserts Sec depending on the elongation factor Tu (EF-Tu). Here, we describe the engineering of EF-Tu for improved selenoprotein synthesis. A Sec-specific selection system was established by expression of human protein O(6)-alkylguanine-DNA alkyltransferase (hAGT), in which the active site cysteine codon has been replaced by the UAG amber codon. The formed hAGT selenoprotein repairs the DNA damage caused by the methylating agent N-methyl-N'-nitro-N-nitrosoguanidine, and thereby enables Escherichia coli to grow in the presence of this mutagen. An EF-Tu library was created in which codons specifying the amino acid binding pocket were randomized. Selection was carried out for enhanced Sec incorporation into hAGT; the resulting EF-Tu variants contained highly conserved amino acid changes within members of the library. The improved UTu-system with EF-Sel1 raises the efficiency of UAG-specific Sec incorporation to >90%, and also doubles the yield of selenoprotein production.

  13. Framework for efficient synthesis of spatially embedded morphologies

    NASA Astrophysics Data System (ADS)

    Vanherpe, Liesbeth; Kanari, Lida; Atenekeng, Guy; Palacios, Juan; Shillcock, Julian

    2016-08-01

    Many problems in science and engineering require the ability to grow tubular or polymeric structures up to large volume fractions within a bounded region of three-dimensional space. Examples range from the construction of fibrous materials and biological cells such as neurons, to the creation of initial configurations for molecular simulations. A common feature of these problems is the need for the growing structures to wind throughout space without intersecting. At any time, the growth of a morphology depends on the current state of all the others, as well as the environment it is growing in, which makes the problem computationally intensive. Neuron synthesis has the additional constraint that the morphologies should reliably resemble biological cells, which possess nonlocal structural correlations, exhibit high packing fractions, and whose growth responds to anatomical boundaries in the synthesis volume. We present a spatial framework for simultaneous growth of an arbitrary number of nonintersecting morphologies that presents the growing structures with information on anisotropic and inhomogeneous properties of the space. The framework is computationally efficient because intersection detection is linear in the mass of growing elements up to high volume fractions and versatile because it provides functionality for environmental growth cues to be accessed by the growing morphologies. We demonstrate the framework by growing morphologies of various complexity.

  14. Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

    PubMed Central

    Matthessen, Roman; Fransaer, Jan; Binnemans, Koen

    2014-01-01

    Summary The near-unlimited availability of CO2 has stimulated a growing research effort in creating value-added products from this greenhouse gas. This paper presents the trends on the most important methods used in the electrochemical synthesis of carboxylic acids from carbon dioxide. An overview is given of different substrate groups which form carboxylic acids upon CO2 fixation, including mechanistic considerations. While most work focuses on the electrocarboxylation of substrates with sacrificial anodes, this review considers the possibilities and challenges of implementing other synthetic methodologies. In view of potential industrial application, the choice of reactor setup, electrode type and reaction pathway has a large influence on the sustainability and efficiency of the process. PMID:25383120

  15. Linchpin dienes: key building-blocks in the synthesis of polyenic frameworks.

    PubMed

    Cornil, J; Guérinot, A; Cossy, J

    2015-04-14

    A myriad of biologically active products incorporates polyenic frameworks. Among the syntheses developed to access these moieties, metal-catalyzed cross-couplings emerged as reactions of choice especially due to their high stereoselectivity. Particularly, the use of bifunctionalized compounds (linchpin reagents) allows a fast, modular and efficient access to polyenic chains. In this review, we will focus on the preparation of bifunctionalized dienes and on their utilization in the synthesis of polyenes.

  16. Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides

    PubMed Central

    2016-01-01

    The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products. PMID:27350334

  17. 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.

  18. Substrate control in stereoselective lanthionine biosynthesis

    NASA Astrophysics Data System (ADS)

    Tang, Weixin; Jiménez-Osés, Gonzalo; Houk, K. N.; van der Donk, Wilfred A.

    2015-01-01

    Enzymes are typically highly stereoselective catalysts that enforce a reactive conformation on their native substrates. We report here a rare example in which the substrate controls the stereoselectivity of an enzyme-catalysed Michael-type addition during the biosynthesis of lanthipeptides. These natural products contain thioether crosslinks formed by a cysteine attack on dehydrated Ser and Thr residues. We demonstrate that several lanthionine synthetases catalyse highly selective anti-additions in which the substrate (and not the enzyme) determines whether the addition occurs from the re or si face. A single point mutation in the peptide substrate completely inverted the stereochemical outcome of the enzymatic modification. Quantum mechanical calculations reproduced the experimentally observed selectivity and suggest that conformational restraints imposed by the amino-acid sequence on the transition states determine the face selectivity of the Michael-type cyclization.

  19. Stereoselective synthesis of ( E)-4-(imidazo[1,2- a]pyrid-2-yl)-3-(4-methylphenylsulfonyl)but-3-en-2-one. X-ray crystal structure and conformational analysis

    NASA Astrophysics Data System (ADS)

    Roche, D.; Force, L.; Carpy, A.; Gardette, D.; Madesclaire, M.

    1998-06-01

    The title compound, gem-ketovinylsulfone 3, was obtained stereoselectively (de > 98%) by the action of the α-anion from p-tolylsulfonylacetone 1 on imidazol[1,2- a]pyridine-2-carbaldehyde 2 in chelation-controlled conditions in the presence of a Lewis acid (ZnCl 2). The X-ray crystal structure of 3 [C 18H 16N 2O 3S: Mt = 340.4, orthorhombic, Pbca, a = 12.208(3) Å, b = 18.848(4) Å, c = 14.566(11) Å, V = 3.351(3) Å3, Z = 8, Dcalc = 1.349 g cm -3, λ( CuKα) = 1.54178 Å, μ = 1.83 mm -1, F(000) = 1424, T = 293 K, R = 0.061 for 2.046 observed reflections] was determined, and confirmed the ( E) configuration. Despite the conjugate position of the vinyl double bond, quasi-coplanar with the imidazopyridine heterocycle, there is no evidence of p-electron delocalization. The crystal cohesion is ensured by a dense network of van der Waals contacts. The conformational analysis of the ( E) and ( Z) stereoisomers was performed by molecular dynamics simulation, and showed the ( E) isomer to be 9.1 kJ mol -1 more stable than the ( Z) isomer.

  20. Utilization of N,N-dialkylcarbamic acid derived from secondary amines and supercritical carbon dioxide: stereoselective synthesis of Z alkenyl carbamates with a CO2-soluble ruthenium-P(OC2H5)3 catalyst.

    PubMed

    Kayaki, Yoshihito; Suzuki, Tomoyuki; Ikariya, Takao

    2008-10-06

    Reversible transformation of diethylamine (1) and supercritical carbon dioxide (scCO(2)) into N,N-diethylcarbamic acid (2) was confirmed by direct acquisition of (1)H and (13)C{(1)H} NMR spectra. The equilibrium between 1+CO(2) and 2 is strongly influenced by conditions of the supercritical state. Low temperature favors formation of carbamic acid, whereas high temperature causes decarboxylation. On the basis of the spectroscopic results of carbamic acid formation under scCO(2) conditions, the ruthenium-catalyzed formation of alkenyl carbamates from terminal alkynes, 1, and carbon dioxide was investigated to demonstrate the useful transformation of elusive carbamic acids. Selectivity toward the CO(2)-fixation products over enynes obtained by dimerization of the alkyne substrates was improved by the use of scCO(2) as a reaction medium. In particular, a CO(2)-soluble ruthenium complex, trans-[RuCl(2){P(OC(2)H(5))(3)}(4)], was found to be effective in affording Z alkenyl carbamates with high stereoselectivity.

  1. Total synthesis of (R,R,R)-α-tocopherol through asymmetric Cu-catalyzed 1,4-addition.

    PubMed

    Termath, Andreas Ole; Sebode, Hanna; Schlundt, Waldemar; Stemmler, René T; Netscher, Thomas; Bonrath, Werner; Schmalz, Hans-Günther

    2014-09-15

    By introducing a disposable activating substituent at C-3, the asymmetric 1,4-addition to a notoriously unreactive 2-substituted chromenone was achieved with high levels of (2R)-stereoselectivity in the presence of a chiral Cu(I)-phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R,R,R)-α-tocopherol from readily available starting materials.

  2. Synthesis of Chiral Aminocyclopropanes by Rare-Earth-Metal-Catalyzed Cyclopropene Hydroamination.

    PubMed

    Teng, Huai-Long; Luo, Yong; Wang, Baoli; Zhang, Liang; Nishiura, Masayoshi; Hou, Zhaomin

    2016-12-05

    The search for efficient and selective routes for the synthesis of chiral aminocyclopropane derivatives is of great interest and importance as these structures are important components of biologically active natural products and pharmaceuticals. We herein report the enantioselective intermolecular hydroamination of substituted cyclopropenes with various amines catalyzed by chiral half-sandwich rare-earth-metal complexes. This method constitutes a 100 % atom-efficient route for the synthesis of a variety of chiral α-aminocyclopropane derivatives in high yields (up to 96 %) and excellent stereoselectivity (up to >20:1 d.r. and 99 % ee) under mild reaction conditions (25 °C).

  3. Palladium-copper catalyzed synthesis of benzofused heterocycles with two heteroatoms: novel and highly regio- and stereoselective syntheses of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles and (E)-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzothiazines.

    PubMed

    Kundu, N G; Nandi, B

    2001-06-29

    A highly novel, general, and convenient palladium and copper-catalyzed procedure has been developed for the synthesis of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40. 3-(2-Aminophenylthio)prop-1-yne 1 reacts with aryl iodides 2-14 under palladium-copper catalysis to yield the disubstituted alkynes 15-27 which after tosylation undergo a novel cyclization with CuI in the presence of triethylamine in THF to (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40 rather than to the expected 3-alkylidene-4-tosyl-3,4-dihydro-2H-1,4-benzothiazines 41. The reaction is highly regio- and stereoselective. The synthesis of 2-(2-arylethyl)-3-tosylbenzothiazolines 42-47, 2-(2-arylvinyl)benzothiazoles 48-54, and a novel 5-substituted uracil derivative 55 of potential biological importance is also being reported. Similarly, the palladium-copper-catalyzed arylation of S-[2-(N-prop-2'-ynyl)aminophenyl]-N,N-dimethylthiocarbamate 58 with aryl iodides yields the disubstituted alkynes 59 which on cyclization with KOH in methanol leads to (E)-2-(2-aryl)methylidene-3,4-dihydro-2H-1,4-benzothiazines 61. The reaction of the diiodo compounds 12-14a, however, with 58 under palladium-copper-catalyzed reactions involves the participation of only one of the iodo groups in the heteroannulation process giving compounds 61i and 61j. These are amenable to further palladium-catalyzed reactions and afford polyunsaturated heteroaromatic compounds 62 and 63.

  4. Theory and modeling of stereoselective organic reactions.

    PubMed

    Houk, K N; Paddon-Row, M N; Rondan, N G; Wu, Y D; Brown, F K; Spellmeyer, D C; Metz, J T; Li, Y; Loncharich, R J

    1986-03-07

    Theoretical investigations of the transition structures of additions and cycloadditions reveal details about the geometries of bond-forming processes that are not directly accessible by experiment. The conformational analysis of transition states has been developed from theoretical generalizations about the preferred angle of attack by reagents on multiple bonds and predictions of conformations with respect to partially formed bonds. Qualitative rules for the prediction of the stereochemistries of organic reactions have been devised, and semi-empirical computational models have also been developed to predict the stereoselectivities of reactions of large organic molecules, such as nucleophilic additions to carbonyls, electrophilic hydroborations and cycloadditions, and intramolecular radical additions and cycloadditions.

  5. Palladium-catalyzed heteroannulation leading to heterocyclic structures with two heteroatoms: a highly regio- and stereoselective synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines.

    PubMed

    Kundu, N G; Chaudhuri, G; Upadhyay, A

    2001-01-12

    A highly convenient method has been developed for the synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines 9 and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines 34-38 through palladium-copper-catalyzed reactions. Aryl halides 7 reacted with 2-[N-alkyl(benzyl)-N-prop-2'-ynyl]aminophenyl tosylate 6 in the presence of (PPh3)2PdCl2 (3 mol %), CuI(5 mol %) in triethylamine at room temperature to yield 2-[N-alkyl(benzyl)-N-(3-aryl-prop-2'-ynyl)]-aminophenyl tosylates 8 in extremely good yields (72-96%). The latter could then be cyclized with KOH in ethanol-water to Z-9 in a highly regio- and stereoselective manner. Similarly, palladium-copper-catalyzed reaction of 2-(prop-2'-ynyloxy)aniline (21) with aryl iodides 7 led to 22-26 which after tosylation and cyclization with cuprous iodide in CH3CN in the presence of K2CO3 and Bu4-NBr led to the (Z)-3-alkyl(aryl)idene-4-tosyl 3,4-dihydro-2H-1,4-benzoxazines 34-38 in good overall yields. The Z-stereochemistry of the products was established from 1H NMR spectra, 3JCH values (between vinylic proton and methylenic carbon of the heterocyclic ring), NOE experiments, and X-ray analysis. The method was also found to be suitable for the synthesis of bis(benzoxazinylated) derivatives 17, 39, and 2-alkyl-3,4-dihydro-2H-1,4-benzoxazines 18. Our method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines is highly efficacious, using easily available starting materials under very mild conditions. Also the synthesis of some novel 5-substituted uracil derivatives 40 and 41 containing the benzoxazinyl moiety and of potential biological interest is being reported.

  6. 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.

  7. A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

    PubMed Central

    Reis, Marcelo Isidoro P; Campos, Vinícius R; Resende, Jackson A L C; Silva, Fernando C

    2015-01-01

    Summary A new and efficient method for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones in one step with high yields from the reaction of lawsone with 1,3,5-triazinanes was developed. PMID:26425181

  8. Asymmetric total synthesis of (+)-bermudenynol, a C15 Laurencia metabolite with a vinyl chloride containing oxocene skeleton, through intramolecular amide enolate alkylation.

    PubMed

    Kim, Gyudong; Sohn, Te-Ik; Kim, Deukjoon; Paton, Robert S

    2014-01-03

    A substrate-controlled asymmetric total synthesis of (+)-bermudenynol, a compact and synthetically challenging C15 Laurencia metabolite that contains several halogen atoms, is reported. The oxocene core, which contains a vinyl chloride, was constructed by an efficient and highly stereoselective intramolecular amide enolate alkylation (IAEA). This result showcases the broad utility of the IAEA methodology as a useful alternative for cases in which the ring-closing metathesis is inefficient.

  9. On the stereoselective aminoacylation of RNA

    NASA Technical Reports Server (NTRS)

    Usher, D. A.; Needels, M. C.

    1984-01-01

    Gabbay and Kleinman (1970) have found that stereospecific complex formation (noncovalent) occurs between nucleic acids and a number of derivatives of amino acids. However, until recently, chiral selection in any nonenzymatic RNA-aminoacylation reaction was unknown. Profy and Usher (1984) reported that aminoacylation of the 'internal' 2-prime-ester occurred with a significant amount of stereoselection. Profy and Usher (1984) have also observed that aminoacylation of the 'internal' 2-prime-hydroxyl groups of polyribonucleotides by the imidazolide of N-3,5-dinitrobenzoylalanine occurs with chiral selection. In order to obtain further information regarding the considered phenomena, a systematic investigation was initiated of the factors which contribute to the observed stereoselectivity of the aminoacylation reaction. In the present paper, the effect of a change in the amino acid from alanine to leucine is considered along with an investigation of the D- and L-alanyl internal' 2-prime esters of the dinucleoside monophosphate of 3-prime,5-prime-ApA.

  10. Efficient and Regioselective Synthesis of β-GalNAc/GlcNAc-Lactose by a Bifunctional Transglycosylating β-N-Acetylhexosaminidase from Bifidobacterium bifidum

    PubMed Central

    Chen, Xiaodi; Xu, Li; Jin, Lan; Sun, Bin; Gu, Guofeng

    2016-01-01

    ABSTRACT β-N-Acetylhexosaminidases have attracted interest particularly for oligosaccharide synthesis, but their use remains limited by the rarity of enzyme sources , low efficiency, and relaxed regioselectivity of transglycosylation. In this work, genes of 13 β-N-acetylhexosaminidases, including 5 from Bacteroides fragilis ATCC 25285, 5 from Clostridium perfringens ATCC 13124, and 3 from Bifidobacterium bifidum JCM 1254, were cloned and heterogeneously expressed in Escherichia coli. The resulting recombinant enzymes were purified and screened for transglycosylation activity. A β-N-acetylhexosaminidase named BbhI, which belongs to glycoside hydrolase family 20 and was obtained from B. bifidum JCM 1254, possesses the bifunctional property of efficiently transferring both GalNAc and GlcNAc residues through β1-3 linkage to the Gal residue of lactose. The effects of initial substrate concentration, pH, temperature, and reaction time on transglycosylation activities of BbhI were studied in detail. With the use of 10 mM pNP-β-GalNAc or 20 mM pNP-β-GlcNAc as the donor and 400 mM lactose as the acceptor in phosphate buffer (pH 5.8), BbhI synthesized GalNAcβ1-3Galβ1-4Glc and GlcNAcβ1-3Galβ1-4Glc at maximal yields of 55.4% at 45°C and 4 h and 44.9% at 55°C and 1.5 h, respectively. The model docking of BbhI with lactose showed the possible molecular basis of strict regioselectivity of β1-3 linkage in β-N-acetylhexosaminyl lactose synthesis. IMPORTANCE Oligosaccharides play a crucial role in many biological events and therefore are promising potential therapeutic agents. However, their use is limited because large-scale production of oligosaccharides is difficult. The chemical synthesis requires multiple protecting group manipulations to control the regio- and stereoselectivity of glycosidic bonds. In comparison, enzymatic synthesis can produce oligosaccharides in one step by using glycosyltransferases and glycosidases. Given the lower price of their glycosyl

  11. Total synthesis of alkyl citrate natural products.

    PubMed

    Rizzacasa, Mark A; Sturgess, Dayna

    2014-03-07

    This review highlights the synthesis of members of the alkyl citrate family of natural products. The focus is on the stereoselective construction of the alkyl citrate moiety common to these compounds.

  12. Total synthesis of haliclamide.

    PubMed

    Gahalawat, Suraksha; Pandey, Satyendra Kumar

    2016-10-04

    A stereoselective approach for the synthesis of haliclamide 1, a marine natural product, has been developed. The notable features of our synthesis include MacMillan cross aldol, Mitsunobu inversion, Yamaguchi-Hirao alkylation, Steglich esterification and macrolactamization reactions and the Corey-Fuchs protocol as the key steps.

  13. Bicyclic proline analogues as organocatalysts for stereoselective aldol reactions: an in silico DFT study.

    PubMed

    Shinisha, C B; Sunoj, Raghavan B

    2007-04-21

    Density functional theory has been employed in investigating the efficiency of a series of bicyclic analogues of proline as stereoselective organocatalysts for the aldol reaction. Three classes of conformationally restricted proline analogues, as part of either a [2.2.1] or [2.1.1] bicyclic framework, have been studied. Transition states for the stereoselective C-C bond formation between enamines derived from [2.2.1] and [2.1.1] bicyclic amino acids and p-nitrobenzaldehyde, leading to enantiomeric products, have been identified. Analysis of the transition state geometries revealed that the structural rigidity of catalysts, improved transition state organization as well as other weak interactions influence the relative stabilities of diastereomeric transition states and help contribute to the overall stereoselectivity in the aldol reaction. These bicyclic catalysts are predicted to be substantially more effective in improving the enantiomeric excess than the widely used organocatalyst proline. Enantiomeric excesses in the range 82-95% are predicted for these bicyclic catalysts when a sterically unbiased substrate such as p-nitrobenzaldehyde is employed for the asymmetric aldol reaction. More interestingly, introduction of substituents, as simple as a methyl group, at the ortho position of the aryl aldehyde bring about an increase in the enantiomeric excess to values greater than 98%. The reasons behind the vital energy separation between diastereomeric transition states has been rationalized with the help of a number of weak interactions such as intramolecular hydrogen bonding and Coulombic interactions operating on the transition states. These predictions could have wider implications for the rational design of improved organocatalysts for stereoselective carbon-carbon bond-forming reactions.

  14. [Efficient synthesis of multisubstituted aromatic compounds from phenol derivatives].

    PubMed

    Ikawa, Takashi

    2014-01-01

    Phenols are abundant in nature and diverse phenols are readily available commercially at low cost. Thus, phenols can be used as the raw materials for the synthesis of valuable multisubstituted aromatic compounds by the direct activation of phenolic hydroxyl groups (C-O bond activation), followed by substitutions with other substituents. Although the derivatization of phenolic hydroxyl groups to sulfonates, such as triflates, nonaflates, tosylates and mesylates, followed by the transition-metal-catalyzed coupling reactions has been extensively investigated for this purpose, the direct C-O bond activation of phenols for subsequent functional group transformation has been a long-standing challenge in modern organic synthesis. In this review, I have summarized my recent studies on the formal direct C-O bond activation of phenols using nonafluorobutanesulfonyl fluoride (NfF) for the synthesis of multisubstituted aromatics. I have focused on the dual use of NfF, a less expensive commercially available reagent, including the tentative formation of highly reactive nonaflates from phenols and the use of the liberated fluoride ion as a nucleophile to promote the reactions of nonaflates. The following four topics are discussed: 1) palladium-catalyzed coupling reactions of phenols, 2) novel preparation of benzynes from 2-silylphenols, 3) synthesis of fluorinated aromatic compounds via the formation of benzynes, and 4) Hiyama coupling of (tert-butyldimethylsilyl)arenes activated by internal phenolic hydroxyl groups.

  15. Theory and modeling of stereoselective organic reactions

    SciTech Connect

    Houk, K.N.; Paddon-Row, M.N.; Rondan, N.G.; Wu, Y.D.; Brown, F.K.; Spellmeyer, D.C.; Metz, J.T.; Li, Y.; Loncharich, R.J.

    1986-03-07

    Theoretical investigations of the transition structures of additions and cycloadditions reveal details about the geometrics of bond-forming processes that are not directly accessible by experiment. The conformational analysis of transition states has been developed from theoretical generalizations about the preferred angle of attack by reagents on multiple bonds and predictions of conformations with respect to partially formed bonds. Qualitative rules for the prediction of the stereochemistries of organic reactions have been devised, and semi-empirical computational models have also been developed to predict the stereoselectivities of reactions of large organic molecules, such as nucleophilic additions to carbonyls, electrophilic hydroborations and cycloadditions, and intramolecular radical additions and cycloadditions. 52 references, 7 figures.

  16. A Novel Implementation of Efficient Algorithms for Quantum Circuit Synthesis

    NASA Astrophysics Data System (ADS)

    Zeller, Luke

    In this project, we design and develop a computer program to effectively approximate arbitrary quantum gates using the discrete set of Clifford Gates together with the T gate (π/8 gate). Employing recent results from Mosca et. al. and Giles and Selinger, we implement a decomposition scheme that outputs a sequence of Clifford, T, and Tt gates that approximate the input to within a specified error range ɛ. Specifically, the given gate is first rounded to an element of Z[1/2, i] with a precision determined by ɛ, and then exact synthesis is employed to produce the resulting gate. It is known that this procedure is optimal in approximating an arbitrary single qubit gate. Our program, written in Matlab and Python, can complete both approximate and exact synthesis of qubits. It can be used to assist in the experimental implementation of an arbitrary fault-tolerant single qubit gate, for which direct implementation isn't feasible.

  17. Efficient synthesis of deuterium labeled hydroxyzine and aripiprazole.

    PubMed

    Vohra, Mohit; Sandbhor, Mahendra; Wozniak, Andrew

    2015-06-15

    Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non-isotopic forms via quantification analysis using HPLC-MS/MS. The synthesis of hydroxyzine-d8 was accomplished by coupling piperazine-d8 with 4-chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2-(2-chloroethoxy) ethanol to afford 11.7% of hydroxyzine-d8 with 99.5% purity. The synthesis of aripiprazole-d8 was also achieved in two steps. 1,4-Dibromobutane-d8 reacted with 7-hydroxy-3,4-dihydro-2(1H)-quinolinone. The first intermediate was then coupled with 1-(2, 3-dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole-d8 with 99.93% purity.

  18. Efficient enantio- and diastereodivergent synthesis of poison-frog alkaloids 251O and trans-223B.

    PubMed

    Toyooka, Naoki; Zhou, Dejun; Nemoto, Hideo; Tezuka, Yasuhiro; Kadota, Shigetoshi; Andriamaharavo, Nirina R; Garraffo, H Martin; Spande, Thomas F; Daly, John W

    2009-09-04

    An efficient and flexible synthesis of poison-frog alkaloids 251O and trans-223B has been achieved by using for both alkaloids an enantiodivergent process starting from the common lactam 1. The relative stereochemistry of 251O and trans-223B was determined to be 7 (R = n-C(7)H(15), R' = n-Pr) and 14 by the present enantioselective synthesis.

  19. Knowledge Based Synthesis of Efficient Structures for Concurrent Computation Using Fat-Trees and Pipelining.

    DTIC Science & Technology

    1986-12-31

    based on the proof is feasible. KES.U.86.11 AFO -Th, 87-0 791 Kestrel Institute Knowledge Based Synthesis of Efficient Structures for Concurrent...manner similar to an assembly line. The proof is a constructive one; a synthesis method based on the proof is feasible. 2 Chapter 2 Introduction This...These techniques are based on the use of closures as a device to schedule commu- nication, resulting from divide and conquer, between halves of a tree

  20. Efficient ytterbium triflate catalyzed microwave-assisted synthesis of 3-acylacrylic acid building blocks.

    PubMed

    Tolstoluzhsky, Nikita V; Gorobets, Nikolay Yu; Kolos, Nadezhda N; Desenko, Sergey M

    2008-01-01

    The derivatives of 4-(hetero)aryl-4-oxobut-2-enoic acid are useful as building blocks in the synthesis of biologically active compounds. An efficient general protocol for the synthesis of these building blocks was developed. This method combines microwave assistance and ytterbium triflate catalyst and allows the fast preparation of the target acids starting from different (hetero)aromatic ketones and glyoxylic acid monohydrate giving pure products in 52-75% isolated yields.

  1. Evolution of an Efficient and Scalable Nine-Step (LLS) Synthesis of Zincophorin Methyl Ester.

    PubMed

    Chen, Liang-An; Ashley, Melissa A; Leighton, James L

    2017-03-07

    Due both to their synthetically challenging and stereochemically complex structures and their wide range of often clinically relevant biological activities, non-aromatic polyketide natural products have for decades attracted an enormous amount of attention from synthetic chemists and played an important role in the development of modern asymmetric synthesis. Often, such compounds are not available in quantity from natural sources, rendering analog synthesis and drug development efforts extremely resource-intensive and time-consuming. In this arena, the quest for ever more step-economical and efficient methods and strategies - useful and important goals in their own right - takes on added importance and the most useful syntheses will combine high levels of step-economy with efficiency and scalability. The non-aromatic polyketide natural product zincophorin methyl ester has attracted significant attention from synthetic chemists due primarily to the historically synthetically challenging C(8)-C(12) all-anti stere-opentad. While great progress has been made in the development of new methodologies to more directly address this problem and as a result in the development of more highly step-economical syntheses, a synthesis that combines high levels of step economy with high levels of efficiency and scalability has remained elusive. To address this problem, we have devised a new synthesis of zincophorin methyl ester that proceeds in just nine steps in the longest linear sequence and proceeds in 10% overall yield. Addition-ally, the scalability and practicability of the route have been demonstrated by performing all of the steps on a meaningful scale. This synthesis thus represents by a significant margin the most step-economical, efficient, and practicable synthesis of this stereochemi-cally complex natural product reported to date, and is well suited to facilitate the synthesis of analogs and medicinal chemistry de-velopment efforts in a time- and resource-efficient

  2. An efficient one-pot four-segment condensation method for protein chemical synthesis.

    PubMed

    Tang, Shan; Si, Yan-Yan; Wang, Zhi-Peng; Mei, Kun-Rong; Chen, Xin; Cheng, Jing-Yuan; Zheng, Ji-Shen; Liu, Lei

    2015-05-04

    Successive peptide ligation using a one-pot method can improve the efficiency of protein chemical synthesis. Although one-pot three-segment ligation has enjoyed widespread application, a robust method for one-pot four-segment ligation had to date remained undeveloped. Herein we report a new one-pot multisegment peptide ligation method that can be used to condense up to four segments with operational simplicity and high efficiency. Its practicality is demonstrated by the one-pot four-segment synthesis of a plant protein, crambin, and a human chemokine, hCCL21.

  3. Stereoselective synthesis of cis-p-menth-8-ene-1,7-diol, cis-p-menthane-1,7-diol, and cis-p-menthane-1,7,8-triol.

    PubMed

    Kobler, Christoph; Effenberger, Franz

    2005-04-22

    The natural products cis-p-menthane-1,7-diol (cis-IV), cis-p-menth-8-ene-1,7-diol (cis-I) and cis-p-menthane-1,7,8-triol (cis-II) are obtained starting from the corresponding cis-cyanohydrins, cis-2 and cis-7, respectively, by chemical transformation of the cyano into the hydroxymethyl group. The key step of the synthesis is the very high cis-selectivity (> or = 96 %) of the MeHNL-catalyzed HCN addition to 4-alkylcyclohexanones. From 4-isopropylcyclohexanone (1) the cyanohydrin cis-2 and from 4-(1-methylvinyl)cyclohexanone (6) the cyanohydrin cis-7 result almost quantitatively. Regioselective hydroxylation of cis-I affords the triol cis-II. X-ray crystal structure determinations of the final products confirm their cis-configuration.

  4. Efficiency, error and yield in light-directed maskless synthesis of DNA microarrays

    PubMed Central

    2011-01-01

    Background Light-directed in situ synthesis of DNA microarrays using computer-controlled projection from a digital micromirror device--maskless array synthesis (MAS)--has proved to be successful at both commercial and laboratory scales. The chemical synthetic cycle in MAS is quite similar to that of conventional solid-phase synthesis of oligonucleotides, but the complexity of microarrays and unique synthesis kinetics on the glass substrate require a careful tuning of parameters and unique modifications to the synthesis cycle to obtain optimal deprotection and phosphoramidite coupling. In addition, unintended deprotection due to scattering and diffraction introduce insertion errors that contribute significantly to the overall error rate. Results Stepwise phosphoramidite coupling yields have been greatly improved and are now comparable to those obtained in solid phase synthesis of oligonucleotides. Extended chemical exposure in the synthesis of complex, long oligonucleotide arrays result in lower--but still high--final average yields which approach 99%. The new synthesis chemistry includes elimination of the standard oxidation until the final step, and improved coupling and light deprotection. Coupling Insertions due to stray light are the limiting factor in sequence quality for oligonucleotide synthesis for gene assembly. Diffraction and local flare are by far the largest contributors to loss of optical contrast. Conclusions Maskless array synthesis is an efficient and versatile method for synthesizing high density arrays of long oligonucleotides for hybridization- and other molecular binding-based experiments. For applications requiring high sequence purity, such as gene assembly, diffraction and flare remain significant obstacles, but can be significantly reduced with straightforward experimental strategies. PMID:22152062

  5. Efficient synthesis of triarylamine-based dyes for p-type dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Wild, Martin; Griebel, Jan; Hajduk, Anna; Friedrich, Dirk; Stark, Annegret; Abel, Bernd; Siefermann, Katrin R.

    2016-05-01

    The class of triarylamine-based dyes has proven great potential as efficient light absorbers in inverse (p-type) dye sensitized solar cells (DSSCs). However, detailed investigation and further improvement of p-type DSSCs is strongly hindered by the fact that available synthesis routes of triarylamine-based dyes are inefficient and particularly demanding with regard to time and costs. Here, we report on an efficient synthesis strategy for triarylamine-based dyes for p-type DSSCs. A protocol for the synthesis of the dye-precursor (4-(bis(4-bromophenyl)amino)benzoic acid) is presented along with its X-ray crystal structure. The dye precursor is obtained from the commercially available 4(diphenylamino)benzaldehyde in a yield of 87% and serves as a starting point for the synthesis of various triarylamine-based dyes. Starting from the precursor we further describe a synthesis protocol for the dye 4-{bis[4‧-(2,2-dicyanovinyl)-[1,1‧-biphenyl]-4-yl]amino}benzoic acid (also known as dye P4) in a yield of 74%. All synthesis steps are characterized by high yields and high purities without the need for laborious purification steps and thus fulfill essential requirements for scale-up.

  6. Efficient synthesis of triarylamine-based dyes for p-type dye-sensitized solar cells

    PubMed Central

    Wild, Martin; Griebel, Jan; Hajduk, Anna; Friedrich, Dirk; Stark, Annegret; Abel, Bernd; Siefermann, Katrin R.

    2016-01-01

    The class of triarylamine-based dyes has proven great potential as efficient light absorbers in inverse (p-type) dye sensitized solar cells (DSSCs). However, detailed investigation and further improvement of p-type DSSCs is strongly hindered by the fact that available synthesis routes of triarylamine-based dyes are inefficient and particularly demanding with regard to time and costs. Here, we report on an efficient synthesis strategy for triarylamine-based dyes for p-type DSSCs. A protocol for the synthesis of the dye-precursor (4-(bis(4-bromophenyl)amino)benzoic acid) is presented along with its X-ray crystal structure. The dye precursor is obtained from the commercially available 4(diphenylamino)benzaldehyde in a yield of 87% and serves as a starting point for the synthesis of various triarylamine-based dyes. Starting from the precursor we further describe a synthesis protocol for the dye 4-{bis[4′-(2,2-dicyanovinyl)-[1,1′-biphenyl]-4-yl]amino}benzoic acid (also known as dye P4) in a yield of 74%. All synthesis steps are characterized by high yields and high purities without the need for laborious purification steps and thus fulfill essential requirements for scale-up. PMID:27196877

  7. Improvement of efficiency in the enzymatic synthesis of lactulose palmitate.

    PubMed

    Bernal, Claudia; Illanes, Andres; Wilson, Lorena

    2015-04-15

    Sugar esters are considered as surfactants due to its amphiphilic balance that can lower the surface tension in oil/water mixtures. Enzymatic syntheses of these compounds are interesting both from economic and environmental considerations. A study was carried out to evaluate the effect of four solvents, temperature, substrate molar ratio, biocatalyst source, and immobilization methodology on the yield and specific productivity of lactulose palmitate monoester synthesis. Lipases from Pseudomonas stutzeri (PsL) and Alcaligenes sp. (AsL), immobilized in porous silica functionalized with octyl groups (adsorption immobilization, OS) and with glyoxyl-octyl groups (both adsorption and covalent immobilization, OGS), were used. The highest lactulose palmitate yields were obtained at 47 °C in acetone, for all biocatalysts, while the best lactulose:palmitic acid molar ratio differed according to the immobilization methodology, being 1:1 for AsL-OGS biocatalyst (20.7 ± 3%) and 1:3 for the others (30-50%).

  8. Rapid and efficient synthesis of α(1-2)mannobiosides.

    PubMed

    Reina, José J; Di Maio, Antonio; Ramos-Soriano, Javier; Figueiredo, Rute C; Rojo, Javier

    2016-03-14

    α(1,2)mannobiosides with different substituents at the reducing end have been synthesized by a common strategy using benzoyls as the permanent protecting groups and an acetyl as the orthogonal protecting group at position C2 of the glycosyl acceptor. The new synthetic strategy has been performed remarkably reducing the number of purification steps, the time of synthesis (less than 72 hours) and improving the overall yield at least three times with respect to the best procedure described in the literature at the moment. Additionally, this protecting group strategy is compatible with the presence of azido groups and the use of Cu catalyzed azide alkyne cycloaddition (CuAAC) also called "click chemistry" for conjugating the α(1-2)mannobiosides to different scaffolds for the preparation of mannosyl multivalent systems.

  9. Ruthenium-catalyzed stereoselective anti-Markovnikov-addition of thioamides to alkynes.

    PubMed

    Goossen, Lukas J; Blanchot, Mathieu; Salih, Kifah S M; Karch, Ralf; Rivas-Nass, Andreas

    2008-10-16

    A catalyst system generated in situ from bis(2-methallyl)-cycloocta-1,5-diene-ruthenium(II) and a phosphine was found to efficiently catalyze the addition of thioamides to terminal alkynes with exclusive formation of the anti-Markovnikov thioenamide products. The stereoselectivity of the addition is usually high and controlled by the choice of the phosphine ligand, whereas the (E)-isomers are predominantly formed in the presence of tri(n-octyl)phosphine, the use of bis(dicyclohexylphosphino)methane preferentially leads to the formation of the (Z)-configured thioenamides.

  10. Stereoselective organocatalytic oxidation of alcohols to enals: a homologation method to prepare polyenes.

    PubMed

    Chen, Xiaobei; Zhang, Yinan; Wan, Huixin; Wang, Wei; Zhang, Shilei

    2016-02-28

    A novel method for organocatalytic oxidation through oxidative enamine catalysis was developed with excellent compatibility for the direct syntheses of enals from simple saturated alcohols. By using this amine-catalyzed IBX-oxidation, a wide range of aromatic and aliphatic substituted enals were successfully generated in high yields and exclusively stereoselective E-geometry. Moreover, varying the solvents and/or the loading amounts of IBX allowed for the selective oxidation of alcohols and aldehydes. Importantly, the homologous application of this method provided a selective and efficient way of preparing various highly sensitive conjugated polyene frameworks, which are enriched in natural products.

  11. Stereoselectivity of presynaptic autoreceptors modulating dopamine release.

    PubMed

    Arbilla, S; Langer, S Z

    1981-12-17

    The effects of the (R)- and (S)-enantiomers of sulpiride and butaclamol were studied on the spontaneous and field stimulation-evoked release of total radioactivity from slices of rabbit caudate nucleus prelabelled with [3H]dopamine. (S)-Sulpiride in concentrations ranging from 0.01--1 microM enhanced the electrically evoked release of [3H]dopamine while (R)-sulpiride was 10 times less potent than (S)-sulpiride. Exposure to (S)-butaclamol (0.01--1 microM) but not to (R)-butaclamol (0.1--10 microM) enhanced the field-stimulated release of [3H]dopamine. The facilitatory effects of (S)- and (R)-sulpiride and (S)-butaclamol on the stimulated release of the labelled neurotransmitter were observed under conditions in which these drugs did not modify the spontaneous outflow of radioactivity. Only the active enantiomers of sulpiride and butaclamol antagonized the inhibition by apomorphine (1 microM) of the stimulated release of [3H]dopamine. Our results indicate that the presynaptic inhibitory dopamine autoreceptors modulating the stimulation-evoked release of [3H]dopamine in the caudate nucleus are, like the classical postsynaptic dopamine receptors, chemically stereoselective.

  12. ACCESS-2: Approximation Concepts Code for Efficient Structural Synthesis, user's guide

    NASA Technical Reports Server (NTRS)

    Miura, H.; Schmit, L. A., Jr.

    1978-01-01

    A user's guide is presented for the ACCESS-2 computer program. ACCESS-2 is a research oriented program which implements a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and general mathematical programming algorithms are applied in the design optimization procedure.

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

    PubMed

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

    2009-01-01

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

  14. Novel and Efficient Synthesis of the Promising Drug Candidate Discodermolide

    DTIC Science & Technology

    2010-02-01

    preparation of the chiral allylic alcohol starting material 12. In the new two-step preparation of 12 (Scheme 6), we avoid the need to prepare a...CH3 OH 12 H2 5% Pd/CaCO3 Pb, quinoline cyclohexane Rather, a chiral propynylzinc reagent is prepared under neutral conditions. Then, a subsequent...that chiral syn, anti stereotriad building blocks may be efficiently accessed from inexpensive starting materials by elaborating a chiral allylic

  15. An efficient prebiotic synthesis of cytosine and uracil

    NASA Technical Reports Server (NTRS)

    Robertson, M. P.; Miller, S. L.

    1995-01-01

    In contrast to the purines, the routes that have been proposed for the prebiotic synthesis of pyrimidines from simple precursors give only low yields. Cytosine can be synthesized from cyanoacetylene and cyanate; the former precursor is produced from a spark discharge in a CH4/N2 mixture and is an abundant interstellar molecule. But this reaction requires relatively high concentrations of cyanate (> 0.1 M), which are unlikely to occur in aqueous media as cyanate is hydrolysed rapidly to CO2 and NH3. An alternative route that has been explored is the reaction of cyanoacetaldehyde (formed by hydrolysis of cyanoacetylene) with urea. But at low concentrations of urea, this reaction produces no detectable quantities of cytosine. Here we show that in concentrated urea solution--such as might have been found in an evaporating lagoon or in pools on drying beaches on the early Earth--cyanoacetaldehyde reacts to form cytosine in yields of 30-50%, from which uracil can be formed by hydrolysis. These reactions provide a plausible route to the pyrimidine bases required in the RNA world.

  16. An Efficient, Optimized Synthesis of Fentanyl and Related Analogs

    PubMed Central

    Valdez, Carlos A.; Leif, Roald N.; Mayer, Brian P.

    2014-01-01

    The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73–78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids. PMID:25233364

  17. Synergy, compatibility, and innovation: merging Lewis acids with stereoselective enamine catalysis.

    PubMed

    Gualandi, Andrea; Mengozzi, Luca; Wilson, Claire M; Cozzi, Pier Giorgio

    2014-04-01

    In recent years there has been an accelerated rate of development in the field of organocatalysis, with asymmetric organocatalysis now reaching full maturity. The invention of new organocatalytic reactions and the exploration of new concepts now appear in tandem with the application of organocatalytic techniques in the synthesis of natural products and active pharmaceutical ingredients (APIs). After a "golden rush" in organocatalysis, researchers are now starting to combine different methods, thereby taking advantage of the significant benefits of synergy. Metals are used in combination with organocatalytic processes, thus reaching complexity that is found in nature, where enzymes take advantage of the presence of certain metals to increase the arsenal of organic transformations available. In this Focus review, we illustrate the possibility of a "happy marriage" between Lewis acids and organocatalytic stereoselective processes. Questions have been raised about the combination of Lewis acids and organocatalysis owing to the presence of water and/or strong bases in these processes. Some Lewis acids have been shown to be compatible with organocatalysis and concepts relating to their use will be illustrated herein. To summarize the fruitful use of Lewis acids in stereoselective organocatalytic processes, we will draw attention to the advantages and selectivity achieved using this method.

  18. Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists

    SciTech Connect

    Eltze, M.; Boer, R.; Sanders, K.H.; Boss, H.; Ulrich, W.R.; Flockerzi, D. )

    1990-01-01

    The biological activity of the (+)-S- and (-)-R-enantiomers of niguldipine, of the (-)-S- and (+)-R-enantiomers of felodipine and nitrendipine, and of rac-nisoldipine and rac-nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)-mimetic U-46619 in guinea pig Langendorff hearts, displacement of (+)-({sup 3}H)isradipine from calcium channel binding sites of guinea pig skeletal muscle T-tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross-contamination was less than 0.5% for both S- and R-enantiomers of niguldipine and nitrendipine and less than 1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)-(S)-/(-)-(R)-niguldipine, (-)-(S)-/(+)-(R)-felodipine, and (-)-(S)-/(+)-(R)-nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio rac-nisoldipine/rac-nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)-(S)-/(-)-(R)-niguldipine = 45 and 35, (-)-(S)-/(+)-(R)-felodipine = 12 and 13, (-)-(S)-/(+)-(R)-nitrendipine = 8 and 8, and rac-nisoldipine/rac-nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U-46619-induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity.

  19. Energetic efficiency of milk synthesis in dual-purpose cows grazing tropical pastures.

    PubMed

    Aguilar-Pérez, Carlos Fernando; Ku-Vera, Juan Carlos; Magaña-Monforte, Juan Gabriel

    2011-04-01

    The aim of this study was to assess the energetic efficiency of milk synthesis by grazing dual-purpose cows with or without a starch-based supplement in tropical South Mexico. Forty-six Holstein × Zebu cows were used in a 2 × 2 × 2 factorial design. Factors analysed were diet (supplemented, unsupplemented), age (young: 1-2 calvings, mature: >3 calvings) and day of lactation (21 and 84 days post-calving). The supplement represented about 30% of estimated dry matter (DM) intake. Grass intake was measured using the n-alkane technique at 21 and 84 days post-calving when calculations of efficiency were performed. Efficiency for milk synthesis was reported as feed conversion efficiency (FCE, kilograms of milk per kilogram of DM intake), gross energetic efficiency (GEE, milk energy output/metabolisable energy (ME) intake) and efficiency of ME use for lactation (k(l), adjusted to zero energy balance). There were no interactions between factors. FCE and GEE were not different between diets, but supplemented cows had a lower (p < 0.01) k(l) value (0.62) than unsupplemented cows (0.67), suggesting a diverted partition of nutrients towards body tissue. Mature cows were more efficient (p < 0.001) than young cows in terms of FCE (1.13 vs 0.87) and GEE (0.34 vs 0.26), but equal in terms of k(l) (0.65). FCE (1.10 vs 0.90) and GEE (0.34 vs 0.27) were both higher on day 21 compared with day 84 post-calving, with a trend for a higher k(l) in early lactation. Dual-purpose cows used tropical grasses efficiently for milk synthesis, and higher milk yield observed in supplemented cows was due to a higher intake of nutrients rather than a higher energetic efficiency.

  20. Stereoselective binding of chiral drugs to plasma proteins.

    PubMed

    Shen, Qi; Wang, Lu; Zhou, Hui; Jiang, Hui-di; Yu, Lu-shan; Zeng, Su

    2013-08-01

    Chiral drugs show distinct biochemical and pharmacological behaviors in the human body. The binding of chiral drugs to plasma proteins usually exhibits stereoselectivity, which has a far-reaching influence on their pharmacological activities and pharmacokinetic profiles. In this review, the stereoselective binding of chiral drugs to human serum albumin (HSA), α1-acid glycoprotein (AGP) and lipoprotein, three most important proteins in human plasma, are detailed. Furthermore, the application of AGP variants and recombinant fragments of HSA for studying enantiomer binding properties is also discussed. Apart from the stereoselectivity of enantiomer-protein binding, enantiomer-enantiomer interactions that may induce allosteric effects are also described. Additionally, the techniques and methods used to determine drug-protein binding parameters are briefly reviewed.

  1. Stereoselective binding of chiral drugs to plasma proteins

    PubMed Central

    Shen, Qi; Wang, Lu; Zhou, Hui; Jiang, Hui-di; Yu, Lu-shan; Zeng, Su

    2013-01-01

    Chiral drugs show distinct biochemical and pharmacological behaviors in the human body. The binding of chiral drugs to plasma proteins usually exhibits stereoselectivity, which has a far-reaching influence on their pharmacological activities and pharmacokinetic profiles. In this review, the stereoselective binding of chiral drugs to human serum albumin (HSA), α1-acid glycoprotein (AGP) and lipoprotein, three most important proteins in human plasma, are detailed. Furthermore, the application of AGP variants and recombinant fragments of HSA for studying enantiomer binding properties is also discussed. Apart from the stereoselectivity of enantiomer-protein binding, enantiomer-enantiomer interactions that may induce allosteric effects are also described. Additionally, the techniques and methods used to determine drug-protein binding parameters are briefly reviewed. PMID:23852086

  2. Synthesis of energy-efficient counters implemented in PLD circuits

    NASA Astrophysics Data System (ADS)

    Kulisz, Józef; Nawrot, Radosław; Kania, Dariusz

    2016-12-01

    The paper presents a comparison of four methods of implementing sequential circuits in Programmable Logic Devices in respect of dissipated power. Objective of the research was to investigate influence of different methods of "disabling" the clock signal on the dynamic power consumed by the circuit. The comparison is carried out using simple counter circuits, i. e. circuits the algorithm of which is described by linear graphs. However, the presented considerations are general, and can be applied to any sequential circuit. Results of simulation tests show that the method based on clock gating is the most efficient one, and it leads to significant reduction of the dissipated dynamic power. The authors also propose a simple modification of global clock network structures, to facilitate clock gating.

  3. Robust and efficient inverse mask synthesis with basis function representation.

    PubMed

    Wu, Xiaofei; Liu, Shiyuan; Lv, Wen; Lam, Edmund Y

    2014-12-01

    Mask optimization is essential in the resolution scaling of optical lithography due to its strong ability to overcome the optical proximity effect. However, it often demands extensive computation in solving the nonlinear optimization problem with a large number of variables. In this paper, we use a set of basis functions to represent the mask patterns, and incorporate this representation into the mask optimization at both the nominal plane and various defocus conditions. The representation coefficients are updated according to the gradient to the coefficients, which can be easily obtained from the gradient to the pixel variables. To ease the computation of the gradient, we use an adaptive method that divides the optimization into two steps, in which a small number of kernels is used as the first step, and more kernels are used for fine optimization. Simulations performed on two test patterns demonstrate that this method can improve the optimization efficiency by several times, and the optimized patterns have better manufacturability compared with regular pixel-based representation.

  4. Information and Efficiency in the Nervous System—A Synthesis

    PubMed Central

    Sengupta, Biswa; Stemmler, Martin B.; Friston, Karl J.

    2013-01-01

    In systems biology, questions concerning the molecular and cellular makeup of an organism are of utmost importance, especially when trying to understand how unreliable components—like genetic circuits, biochemical cascades, and ion channels, among others—enable reliable and adaptive behaviour. The repertoire and speed of biological computations are limited by thermodynamic or metabolic constraints: an example can be found in neurons, where fluctuations in biophysical states limit the information they can encode—with almost 20–60% of the total energy allocated for the brain used for signalling purposes, either via action potentials or by synaptic transmission. Here, we consider the imperatives for neurons to optimise computational and metabolic efficiency, wherein benefits and costs trade-off against each other in the context of self-organised and adaptive behaviour. In particular, we try to link information theoretic (variational) and thermodynamic (Helmholtz) free-energy formulations of neuronal processing and show how they are related in a fundamental way through a complexity minimisation lemma. PMID:23935475

  5. Efficient enzymatic synthesis of ampicillin by mutant Alcaligenes faecalis penicillin G acylase.

    PubMed

    Deng, Senwen; Su, Erzheng; Ma, Xiaoqiang; Yang, Shengli; Wei, Dongzhi

    2015-04-10

    Semi-synthetic β-lactam antibiotics (SSBAs) are one of the most important antibiotic families in the world market. Their enzymatic synthesis can be catalyzed by penicillin G acylases (PGAs). In this study, to improve enzymatic synthesis of ampicillin, site-saturating mutagenesis was performed on three conserved amino acid residues: βF24, αR146, and αF147 of thermo-stable penicillin G acylase from Alcaligenes faecalis (Af PGA). Four mutants βF24G, βF24A, βF24S, and βF24P were recovered by screening the mutant bank. Kinetic analysis of them showed up to 800-fold increased kcat/Km value for activated acyl donor D-phenylglycine methyl ester (D-PGME). When βF24G was used for ampicillin synthesis under kinetic control at industrially relevant conditions, 95% of nucleophile 6-aminopenicillanic acid (6-APA) was converted to ampicillin in aqueous medium at room temperature while 12% process time is needed to reach maximum product accumulation at 25% enzyme concentration compared with the wild-type Af PGA. Consequently, process productivity of enzymatic synthesis of ampicillin catalyzed by Af PGA was improved by more than 130 times, which indicated an enzyme viable for efficient SSBAs synthesis.

  6. Stereoselective formation of a 2 prime (3 prime)- aminoacyl ester of a nucleotide

    NASA Technical Reports Server (NTRS)

    Weber, A. L.

    1986-01-01

    Reaction of DL-series and adenosine-5-phosphorimidazolide in the presence of adenosine-5'-(0-methylphosphate) and imidazole resulted in the stereoselective synthesis of the aminoacyl nucleotide ester, 2'(3')-0-seryl-adenosine-5'-(0-methylphosphate). The enantiomeric excess of D-serine incorporated into 2'(3')-0-seryl-adenosine-5'-(0-methylphosphate) was about 9%. Adenylyl-(5->N)-serine and an unknown product also incorporated an excess of D-serine, however, seryl-serine showed an excess of L-serine. The relationship of these results to the origin of the biological pairing of L-amino acids and nucleotides containing D-ribose is discussed.

  7. Z-Stereoselective Aza-Peterson Olefinations with Bis(trimethylsilane) Reagents and Sulfinyl Imines.

    PubMed

    Das, Manas; O'Shea, Donal F

    2016-01-15

    Highly stereoselective aza-Peterson olefinations from bench-stable α,α-bis(trimethylsilyl)toluene reagents and N-substituted imines have been achieved using TMSO(-)/Bu4N(+) as Lewis base activator in THF. Remarkably, and for the first time, N-t-butanesulfinyl imines were utilized for the synthesis of Z-stilbenes with excellent selectivities, while N-aryl imines generated E-stilbenes under identical reaction conditions. The protocol proved general for numerous examples with low molecular weight byproducts formed. The origin of the Z-selectivity is proposed to be a result of diastereoselective addition to N-t-butanesulfinyl imines followed by syn-elimination of an in situ formed hypervalent silicate.

  8. A coenzyme-independent decarboxylase/oxygenase cascade for the efficient synthesis of vanillin.

    PubMed

    Furuya, Toshiki; Miura, Misa; Kino, Kuniki

    2014-10-13

    Vanillin is one of the most widely used flavor compounds in the world as well as a promising versatile building block. The biotechnological production of vanillin from plant-derived ferulic acid has attracted much attention as a new alternative to chemical synthesis. One limitation of the known metabolic pathway to vanillin is its requirement for expensive coenzymes. Here, we developed a novel route to vanillin from ferulic acid that does not require any coenzymes. This artificial pathway consists of a coenzyme-independent decarboxylase and a coenzyme-independent oxygenase. When Escherichia coli cells harboring the decarboxylase/oxygenase cascade were incubated with ferulic acid, the cells efficiently synthesized vanillin (8.0 mM, 1.2 g L(-1) ) via 4-vinylguaiacol in one pot, without the generation of any detectable aromatic by-products. The efficient method described here might be applicable to the synthesis of other high-value chemicals from plant-derived aromatics.

  9. Nano Clinoptilolite: Highly Efficient Catalyst for the Synthesis of Chromene Derivatives Under Solvent-Free Conditions.

    PubMed

    Hallajian, Sara; Khalilzadeh, Mohammad A; Tajbakhsh, Mahgol; Alipour, Eskandar; Safaei, Zahra

    2015-01-01

    An efficient and selective synthesis of substituted chromene derivatives via three-component reaction of 4-hydroxycoumarin or 1,3-dicarbonyl compounds, activated acetylenic compounds and N-nucleophiles is described. The reaction was conducted under solvent-free conditions at 70°C using potassium fluoride impregnated on natural zeolite as a cheap and available solid base. The procedure has several advantages involving selectivity, excellent yields and a convenient work-up method.

  10. ACCESS 1: Approximation Concepts Code for Efficient Structural Synthesis program documentation and user's guide

    NASA Technical Reports Server (NTRS)

    Miura, H.; Schmit, L. A., Jr.

    1976-01-01

    The program documentation and user's guide for the ACCESS-1 computer program is presented. ACCESS-1 is a research oriented program which implements a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and general mathematical programming algorithms are applied in the design optimization procedure. Implementation of the computer program, preparation of input data and basic program structure are described, and three illustrative examples are given.

  11. An efficient and convenient palladium catalyst system for the synthesis of amines from allylic alcohols.

    PubMed

    Banerjee, Debasis; Jagadeesh, Rajenahally V; Junge, Kathrin; Junge, Henrik; Beller, Matthias

    2012-10-01

    A novel catalyst system for efficient amination of allylic alcohols with aryl and alkyl amines is presented. By applying a convenient combination consisting of Pd(OAc)(2)/1,10-phenanthroline, a variety of allylic alcohols reacted smoothly to give the corresponding secondary and tertiary amines in good to excellent yields with high regioselectivity. The usefulness of our protocol is demonstrated in the one-step synthesis of the antifungal drug naftifine and the calcium channel blocker flunarizine.

  12. Efficient and convenient synthesis of indazol-3(2H)-ones and 2-aminobenzonitriles.

    PubMed

    Dou, Guolan; Shi, Daqing

    2009-01-01

    A mild, efficient, one-pot protocol for the synthesis of indazole-3(2H)-ones via cyclization of nitro-aryl substrates through low-valent titanium reagent has been described. The method used Triethylamine (TEA) to control pH. Particularly, 2-aminobenzonitriles were synthesized by one step easily. The mechanistic course of the reaction suggests the involvement of an anion leading to an intramolecular cyclization via N-N bond formation.

  13. 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.

  14. High stereoselectivity on low temperature Diels-Alder reactions

    PubMed Central

    da Silva Filho, Luiz Carlos; Lacerda Júnior, Valdemar; Constantino, Mauricio Gomes; da Silva, Gil Valdo José; Invernize, Paulo Roberto

    2005-01-01

    We have found that some of the usually poor dienophiles (2-cycloenones) can undergo Diels-Alder reaction at -78°C with unusually high stereoselectivity in the presence of niobium pentachloride as a Lewis acid catalyst. A remarkable difference in reaction rates for unsubstituted and α- or β-methyl substituted 2-cycloenones was also observed. PMID:16542029

  15. Dynamic Origin of the Stereoselectivity of a Nucleophilic Substitution Reaction

    PubMed Central

    Bogle, Xavier S.; Singleton, Daniel A.

    2012-01-01

    A nucleophilic substitution on a dichlorovinyl ketone was studied experimentally and computationally. A mixture of products is observed experimentally, but a conventional computational analysis does not account for the formation of the minor stereoisomer. Instead, the product mixture is predicted accurately from a dynamic trajectory study on a bifurcating energy surface. The dynamic origin of the stereoselectivity of the reaction is discussed. PMID:22540965

  16. Directed evolution of leucine dehydrogenase for improved efficiency of L-tert-leucine synthesis.

    PubMed

    Zhu, Lin; Wu, Zhe; Jin, Jian-Ming; Tang, Shuang-Yan

    2016-07-01

    L-tert-Leucine and its derivatives are used as synthetic building blocks for pharmaceutical active ingredients, chiral auxiliaries, and ligands. Leucine dehydrogenase (LeuDH) is frequently used to prepare L-tert-leucine from the α-keto acid precursor trimethylpyruvate (TMP). In this study, a high-throughput screening method for the L-tert-leucine synthesis reaction based on a spectrophotometric approach was developed. Directed evolution strategy was applied to engineer LeuDH from Lysinibacillus sphaericus for improved efficiency of L-tert-leucine synthesis. After two rounds of random mutagenesis, the specific activity of LeuDH on the substrate TMP was enhanced by more than two-fold, compared with that of the wild-type enzyme, while the activity towards its natural substrate, leucine, decreased. The catalytic efficiencies (k cat/K m) of the best mutant enzyme, H6, on substrates TMP and NADH were all enhanced by more than five-fold as compared with that of the wild-type enzyme. The efficiency of L-tert-leucine synthesis by mutant H6 was significantly improved. A productivity of 1170 g/l/day was achieved for the mutant enzyme H6, compared with 666 g/l/day for the wild-type enzyme.

  17. Collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol: application of the organocatalytic [4+3] cycloaddition reaction.

    PubMed

    Wang, Jie; Chen, Shu-Guang; Sun, Bing-Feng; Lin, Guo-Qiang; Shang, Yong-Jia

    2013-02-11

    The concise collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol has been accomplished in 10-15 steps, with the total synthesis of orientalol E and oxyphyllol being achieved for the first time. The success obtained was enabled by the realization of the [4+3] cycloaddition reaction of 9 and 10. Other features of the synthesis include 1) the intramolecular Heck reaction to access the azulene core, 2) the epoxidation-S(N)2' reduction sequence to access the allylic alcohol, 3) the efficient regioselective and stereoselective formal hydration of the bridging C=C bond in the synthesis of englerins, and 4) the late-stage chemo- and stereoselective C-H oxidation in the synthesis of orientalol E. The total synthesis of these natural products has enabled the structural revision of oxyphyllol and established the absolute stereochemical features of the organocatalytic [4+3] cycloaddition reaction. The identification of 5 as the natural product oxyphyllol, the success in converting 5 to orientalol E, along with the fact that englerins and oxyphyllol were isolated from plants of the same genus Phyllanthus gives support to our proposed biosynthetic pathways. This work may enable detailed biological evaluations of these natural products and their analogues and derivatives, especially of their potential in the fight against renal cell carcinoma (RCC).

  18. A new structural analysis/synthesis capability - ACCESS. [Approximation Concepts Code for Efficient Structural Synthesis

    NASA Technical Reports Server (NTRS)

    Schmit, L. A.; Miura, H.

    1975-01-01

    The creation of an efficient automated capability for minimum weight design of structures is reported. The ACCESS 1 computer program combines finite element analysis techniques and mathematical programming algorithms using an innovative collection of approximation concepts. Design variable linking, constraint deletion techniques and approximate analysis methods are used to generate a sequence of small explicit mathematical programming problems which retain the essential features of the design problem. Organization of the finite element analysis is carefully matched to the design optimization task. The efficiency of the ACCESS 1 program is demonstrated by giving results for several example problems.

  19. Stereoselective synthesis and molecular modeling of chiral cyclopentanes.

    PubMed

    Abdel-Jalil, Raid J; Steinbrecher, Thomas; Al-Harthy, Thuraya; Mahal, Ahmed; Abou-Zied, Osama K; Voelter, Wolfgang

    2015-10-13

    The reaction of 3-methyseleno-2-methylselenomethyl-propene with benzyl 2,3-anhydro-4-O-triflyl-β-L-ribopyranoside provides a major convenient enantiomeric product of 1-methylene-(benzyl3,4-dideoxy-α-D-arabinopyranoso)-[3,4-c]-cyclopentane, with benzyl-2,3-anhydro-4-deoxy-4-C-(2-methyl- propen-3-yl)-α-D-lyxopyranoside as a minor product. While the reaction of 3-methyseleno-2-[methylselenomethyl]-propene with benzyl 2,3-anhydro-4-O-triflyl-α-D-ribopyranoside produces a good yield of benzyl-2,3-anhydro-4-deoxy-4-C-(2-methylpropen-3-yl)-α-D-lyxo-pyranoside. Molecular modeling and molecular dynamics simulations indicate that the intermediate in the reaction of the β-L sugar frequently occupies an optimal conformation that leads to the formation of cyclopentane, while the intermediate in the reaction of the α-D sugar has a very small probability. The results point to the dominant role of the β-L sugar intermediate in controlling the cyclopentane formation.

  20. Stereoselective Synthesis of Spirooxindole Amides through Nitrile Hydrozirconation

    PubMed Central

    Lu, Chunliang; Xiao, Qing; Floreancig, Paul E.

    2010-01-01

    Spirooxindole amides can be prepared by the intramolecular addition of functionalized indoles into acyliminium ions that are accessed from nitriles by hydrozirconation and acylation. The stereochemical outcome at the quaternary center was controlled by the steric bulk of the substituent at the 2-position of the indole unit. The products are well-suited for diversification to prepare libraries. PMID:20961073

  1. A SHORT, STEREOSELECTIVE SYNTHESIS OF NEO-INOSITOL. (R826113)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. Simplified Application of Material Efficiency Green Metrics to Synthesis Plans: Pedagogical Case Studies Selected from "Organic Syntheses"

    ERIC Educational Resources Information Center

    Andraos, John

    2015-01-01

    This paper presents a simplified approach for the application of material efficiency metrics to linear and convergent synthesis plans encountered in organic synthesis courses. Computations are facilitated and automated using intuitively designed Microsoft Excel spreadsheets without invoking abstract mathematical formulas. The merits of this…

  3. Studies on a urea-directed Stork-Crabtree hydrogenation. Synthesis of the C1-C9 subunit of (+)-zincophorin.

    PubMed

    Song, Zhenlei; Hsung, Richard P; Lu, Ting; Lohse, Andrew G

    2007-12-07

    A detailed account on the stereoselective synthesis of the C1-C9 subunit of (+)-zincophorin is described here. This approach features the first application of a stereoselective inverse electron demand hetero-[4 + 2] cycloaddition of chiral allenamides in natural product synthesis. The C1-C9 subunit matches Cossy's intermediate, thereby constituting a formal total synthesis. In addition, details of an unusual urea-directed Stork-Crabtree hydrogenation observed during these efforts are also disclosed here.

  4. Steric stabilization of Pickering emulsions for the efficient synthesis of polymeric microcapsules.

    PubMed

    Salari, Joris W O; van Heck, Jeroen; Klumperman, Bert

    2010-09-21

    It is commonly known that Pickering emulsions are extremely stable against coalescence and are, therefore, potentially interesting for the synthesis of new materials, such as colloidosomes, microcapsules, composite particles, foams, and so on. However, for the efficient synthesis of such materials, one also has to consider the colloidal stability against aggregation, which is often neglected. In this study, it is demonstrated that steric stabilization is provided to Pickering emulsion droplets by the adsorption of poly(styrene-block-ethylene-co-propylene) (pS-b-EP) and that it is a requirement for the efficient synthesis of polymeric microcapsules. Monodisperse polystyrene particles of 648 nm are synthesized by soap-free emulsion polymerization. A model Pickering emulsion is then formed by the addition of sodium chloride at a critical concentration of 325 mM and mixing it with either heptane or decane. Subsequently, pS-b-EP is added to the Pickering emulsion to provide steric stabilization. Size exclusion chromatography is used to prove and quantify the adsorption of pS-b-EP onto the Pickering emulsion droplets. A maximum surface coverage of 1.3 mg/m(2) is obtained after 2 h, which is approximately one-third of the adsorption on a pure pS surface. We believe that the presence of polar sulfate groups on the particle, which initially stabilized the particle in water, reduces the adsorption of pS-b-EP. Microcapsules are formed by heating the Pickering emulsion above the glass-transition temperature of the particles. Significant aggregation is observed, if no pS-b-EP is used. The adsorption of pS-b-EP provides steric stabilization to the Pickering emulsion droplets, reduces aggregation significantly, and ultimately leads to the successful and efficient synthesis of pS microcapsules.

  5. High-efficient Synthesis of Graphene Oxide Based on Improved Hummers Method

    NASA Astrophysics Data System (ADS)

    Yu, Huitao; Zhang, Bangwen; Bulin, Chaoke; Li, Ruihong; Xing, Ruiguang

    2016-11-01

    As an important precursor and derivate of graphene, graphene oxide (GO) has received wide attention in recent years. However, the synthesis of GO in an economical and efficient way remains a great challenge. Here we reported an improved NaNO3-free Hummers method by partly replacing KMnO4 with K2FeO4 and controlling the amount of concentrated sulfuric acid. As compared to the existing NaNO3-free Hummers methods, this improved routine greatly reduces the reactant consumption while keeps a high yield. The obtained GO was characterized by various techniques, and its derived graphene aerogel was demonstrated as high-performance supercapacitor electrodes. This improved synthesis shows good prospects for scalable production and applications of GO and its derivatives.

  6. Efficient synthesis of silver nanoparticles from Prosopis juliflora leaf extract and its antimicrobial activity using sewage

    NASA Astrophysics Data System (ADS)

    Raja, K.; Saravanakumar, A.; Vijayakumar, R.

    2012-11-01

    In this paper, aqueous extract of fresh leaves of Prosopis juliflora was used for the synthesis of silver (Ag) nanoparticles. UV-Vis spectroscopy studies were carried out to asses silver nanoparticles formation within 5 min, scanning electron microscopic was used to characterize shape of the Ag nanoparticles, X-ray diffraction analysis confirms the nanoparticles as crystalline silver and facecentered cubic type and Fourier transform infra-red assed that shows biomolecule compounds which are responsible for reduction and capping material of silver nanoparticles. The anti microbial activity of silver nanoparticle was performed using sewage. The approach of plant-mediated synthesis appears to be cost efficient, eco-friendly and easy methods.

  7. Efficient synthesis of silver nanoparticles from Prosopis juliflora leaf extract and its antimicrobial activity using sewage.

    PubMed

    Raja, K; Saravanakumar, A; Vijayakumar, R

    2012-11-01

    In this paper, aqueous extract of fresh leaves of Prosopis juliflora was used for the synthesis of silver (Ag) nanoparticles. UV-Vis spectroscopy studies were carried out to asses silver nanoparticles formation within 5 min, scanning electron microscopic was used to characterize shape of the Ag nanoparticles, X-ray diffraction analysis confirms the nanoparticles as crystalline silver and facecentered cubic type and Fourier transform infra-red assed that shows biomolecule compounds which are responsible for reduction and capping material of silver nanoparticles. The anti microbial activity of silver nanoparticle was performed using sewage. The approach of plant-mediated synthesis appears to be cost efficient, eco-friendly and easy methods.

  8. High-efficient Synthesis of Graphene Oxide Based on Improved Hummers Method

    PubMed Central

    Yu, Huitao; Zhang, Bangwen; Bulin, Chaoke; Li, Ruihong; Xing, Ruiguang

    2016-01-01

    As an important precursor and derivate of graphene, graphene oxide (GO) has received wide attention in recent years. However, the synthesis of GO in an economical and efficient way remains a great challenge. Here we reported an improved NaNO3-free Hummers method by partly replacing KMnO4 with K2FeO4 and controlling the amount of concentrated sulfuric acid. As compared to the existing NaNO3-free Hummers methods, this improved routine greatly reduces the reactant consumption while keeps a high yield. The obtained GO was characterized by various techniques, and its derived graphene aerogel was demonstrated as high-performance supercapacitor electrodes. This improved synthesis shows good prospects for scalable production and applications of GO and its derivatives. PMID:27808164

  9. Total synthesis of racemic and (R) and (S)-4-methoxyalkanoic acids and their antifungal activity.

    PubMed

    Das, Biswanath; Shinde, Digambar Balaji; Kanth, Boddu Shashi; Kamle, Avijeet; Kumar, C Ganesh

    2011-07-01

    The total synthesis of 4-methoxydecanoic acid and 4-methoxyundecanoic acid in racemic and stereoselective [(R) and (S)] forms has been accomplished. For stereoselective synthesis of the compounds (S) and (R)-BINOL complexes have been used to generate the required chiral centres. The antifungal activity of these compounds has been studied against different organisms and the results were found to be impressive. The activity of the compounds in racemic and in stereoselective forms was compared. (R)-4-Methoxydecanoic acid was found to be most potent (MIC: 0.019 mg/mL against Candida albicans MTCC 227, C. albicans MTCC 4748, Aspergillus brasiliensis (niger) MTCC 281 and Issatchenkia orientalis MTCC 3020).

  10. Rational design and synthesis of freestanding photoelectric nanodevices as highly efficient photocatalysts.

    PubMed

    Qu, Yongquan; Liao, Lei; Cheng, Rui; Wang, Yue; Lin, Yung-Chen; Huang, Yu; Duan, Xiangfeng

    2010-05-12

    Photocatalysts are of significant interest in solar energy harvesting and conversion into chemical energy. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here we report the rational design of a new generation of freestanding photoelectric nanodevices as highly efficient and stable photocatalysts by integrating a nanoscale photodiode with two redox catalysts in a single nanowire heterostructure. We show that a platinum-silicon-silver nanowire heterostructure can be synthesized to integrate a nanoscale metal-semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. We further demonstrated that the Schottky diodes exhibited a pronounced photovoltaic effect with nearly unity internal quantum efficiency and that the integrated nanowire heterostructures could be used as highly efficient photocatalysts for a wide range of thermodynamically downhill and uphill reactions including the photocatalytic degradation of organic dyes and the reduction of metal ions and carbon dioxide using visible light. Our studies for the first time demonstrated the integration of multiple distinct functional components into a single nanostructure to form a standalone active nanosystem and for the first time successfully realized a photoelectric nanodevice that is both highly efficient and highly stable throughout the entire solar spectrum. It thus opens a rational avenue to the design and synthesis of a new generation of photoelectric nanosystems with unprecedented efficiency and stability and will have a broad impact in areas including environmental remediation, artificial photosynthesis and solar fuel production.

  11. Carbon dioxide mediated stereoselective copper-catalyzed reductive coupling of alkynes and thiols.

    PubMed

    Riduan, Siti Nurhanna; Ying, Jackie Y; Zhang, Yugen

    2012-04-06

    A simple protocol for the stereoselective copper-catalyzed hydrothiolation of alkynes under a CO(2) atmosphere has been developed. The stereoselectivity is determined by the presence/absence of a CO(2) atmosphere. The reaction system is robust and utilizes inexpensive, readily available substrates. A cyclic alkene/carboxylate copper complex intermediate is proposed as the key step in determining the stereoselectivity, and an equivalent amount of water is found to play an active role as a proton donor.

  12. Stereoselective propranolol metabolism in two drug induced rat hepatic microsomes.

    PubMed

    Li, Xin; Zeng, Su

    2000-02-01

    AIM:To study the influence of inducers BNF and PB on the stereoselective metabolism of propranolol in rat hepatic microsomes.METHODS:Phase I metabolism of propranolol was studied by using the microsomes induced by BNF and PB and the non induced microsome as the control.The enzymatic kinetic parameters of propranolol enantiomers were calculated by regression analysis of Lineweaver-Burk plots. Propranolol concentrations were assayed by HPLC.RESULTS:A RP-HPLC method was developed to determine propranolol concentration in rat hepatic microsomes. The linearity equations for R(+)propranolol and S(-) propranolol were A = 705.7C+311.2C (R = 0.9987) and a = 697.2C+311.4C (R = 0.9970) respectively. Recoveries of each enantiomer were 98.9%, 99.5%, 101.0% at 60&mgr;mol/L, 120&mgr;mol/L, 240&mgr;mol/L respectively. At the concentration level of 120&mgr;mol/L, propranolol enantiomers were metabolized at different rates in different microsomes. The concentration ratio R(+)/S(-) of control and PB induced microsomes increased with time, whereas that of microsome induced by BNF decreased. The assayed enzyme parameters were: 1. Km. Control group: R(+)30 plus minus 8, S(-)18 plus minus 5; BNF group: R(+)34 plus minus 3, S(-)39 plus minus 7; PB group: R(+)38 plus minus 17, S(-)36 plus minus 10. 2. Vmax. Control group: R(+)1.5 plus minus 0.2, S(-)2.9 plus minus 0.3; BNF group: R(+)3.8 plus minus 0.3, S(-)3.3 plus minus 0.5; PB group: R(+)0.07 plus minus 0.03, S(-)1.94 plus minus 0.07. 3. Clint. Control group: R(+)60 plus minus 3, S(-)170 plus minus 30; BNF group: R(+)111.0 plus minus 1, S(-) 84 plus minus 5; PB group: R(+)2.0 plus minus 2, S(-)56.0 plus minus 1. The enzyme parameters compared with unpaired t tests showed that no stereoselectivity was observed in enzymatic affinity of three microsomes to enantiomers and their catalytic abilities were quite different and had stereoselectivities.Compared with the control, microsome induced by BNF enhanced enzyme activity to propranolol R

  13. A Sustainable and Efficient Synthesis of Benzyl Phosphonates Using PEG/KI Catalytic System

    PubMed Central

    Disale, Shamrao; Kale, Sandip; Abraham, George; Kahandal, Sandeep; Sawarkar, Ashish N.; Gawande, Manoj B.

    2016-01-01

    An efficient and expedient protocol for the synthesis of benzyl phosphonates using KI/K2CO3 as a catalytic system and PEG-400 as benign solvent has been developed. The reaction proceeds smoothly at room temperature achieving excellent selectivity and yield of the corresponding products. The combination of PEG-400, KI, and K2CO3 in this reaction avoids the need of volatile/toxic organic solvents and reactive alkali metals or metal nanoparticles/hydrides. We believe that this benign combination (PEG-400 and KI) could be used for other related organic transformations. PMID:27579301

  14. An efficient protocol for the solid-phase synthesis of glycopeptides under microwave irradiation.

    PubMed

    Garcia-Martin, Fayna; Hinou, Hiroshi; Matsushita, Takahiko; Hayakawa, Shun; Nishimura, Shin-Ichiro

    2012-02-28

    A standardized and smooth protocol for solid-phase glycopeptides synthesis under microwave irradiation was developed. Double activation system was proved to allow for highly efficient coupling of Tn-Ser/Thr and bulky core 2-Ser/Thr derivatives. Versatility and robustness of the present strategy was demonstrated by constructing a Mucine-1 (MUC1) fragment and glycosylated fragments of tau protein. The success of this approach relies on the combination of microwave energy, a resin consisting totally of polyethylene glycol, a low excess of sugar amino acid and the "double activation" method.

  15. ZnO Catalyzed Efficient Synthesis of Some New 2-Substituted-4,6-diarylpyrimidines

    PubMed Central

    Ameta, K. L.; Kumar, Biresh; Rathore, Nitu S.

    2012-01-01

    A simple and efficient protocol is developed for the synthesis of 2-substituted-4,6-diarylpyrimidines from one-pot three-component reaction of 4′-hydroxy-3′,5′-dinitro substituted chalcones, S-benzylthiouronium chloride (SBT), and heterocyclic secondary amines (morpholine/pyrrolidine/piperidine) in the presence of 15 mol% of ZnO as a heterogeneous catalyst. The present methodology offers several advantages such as being a simple procedure as well as providing excellent yields, and short reaction time. The catalyst is inexpensive, stable, and can be easily recycled and reused for several cycles with consistent activity. PMID:24052838

  16. A sustainable and efficient synthesis of benzyl phosphonates using PEG/KI catalytic system

    NASA Astrophysics Data System (ADS)

    Gawande, Manoj; Disale, Shamrao; Kale, Sandip; Abraham, George; Kahandal, Sandeep; Sawarkar, Ashish

    2016-08-01

    An efficient and expedient protocol for the synthesis of benzyl phosphonates using KI/K2CO3 as a catalytic system and PEG-400 as benign solvent has been developed. The reaction proceeds smoothly at room temperature achieving excellent selectivity and yield of the corresponding products. The combination of PEG-400, KI and K2CO3 in this reaction avoids the need of volatile/toxic organic solvents and reactive alkali metals or metal nanoparticles/hydrides. We believe that this benign combination (PEG-400 and KI) could be used for other related organic transformations.

  17. A highly efficient green synthesis of 1, 8-dioxo-octahydroxanthenes

    PubMed Central

    2011-01-01

    SmCl3 (20 mol%) has been used as an efficient catalyst for reaction between aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione at 120°C to give 1,8-dioxo-octahydroxanthene derivatives in high yield. The same reaction in water, at room temperature gave only the open chain analogue of 1,8-dioxo-octahydroxanthene. Use of eco-friendly green Lewis acid, readily available catalyst and easy isolation of the product makes this a convenient method for the synthesis of either of the products. PMID:22152051

  18. An efficient synthesis method targeted to marine alkaloids marinacarbolines A-D and their antitumor activities.

    PubMed

    Li, Jun; Tang, Yang; Jin, Hui-Juan; Cui, Yi-Di; Zhang, Li-Juan; Jiang, Tao

    2015-01-01

    Marinacarbolines A-D are a series of marine β-carboline alkaloids isolated from actinomycete Marinactinospora thermotolerans of the deep South China Sea with antiplasmodial activities. In inhibition assays of in vitro growth of Plasmodium falciparum, marinacarbolines exhibited antiplasmodial activity against drug-sensitive line 3D7 and drug-resistant line Dd2 of P. falciparum. However, approaches for the synthesis of such useful compounds are very limited. In this work, we reported a simple, efficient, and versatile process to synthesize marinacarbolines A-D (1-4). On the basis of that, the antitumor activities of marinacarbolines in a structure-dependent manner were allowed to be unveiled.

  19. An Efficient Synthesis of 2-Substituted Benzimidazoles via Photocatalytic Condensation of o-Phenylenediamines and Aldehydes.

    PubMed

    Kovvuri, Jeshma; Nagaraju, Burri; Kamal, Ahmed; Srivastava, Ajay K

    2016-10-10

    A photocatalytic method has been developed for the efficient synthesis of functionalized benzimidazoles. This protocol involves photocatalytic condensation of o-phenylenediamines with various aldehydes using the Rose Bengal as photocatalyst. The method was found to be general and was successfully employed for accessing pharmaceutically important benzimidazoles by the condensation of aromatic, heteroaromatic and aliphatic aldehydes with o-phenylenediamines, in good-to-excellent yields. Notably, the method was found to be effective for the condensation of less reactive heterocyclic aldehydes with o-phenylenediamines.

  20. Molecular basis for the substrate stereoselectivity in Tryptophan Dioxygenase

    PubMed Central

    Capece, Luciana; Lewis-Ballester, Ariel; Marti, Marcelo A.; Estrin, Dario A.; Yeh, Syun-Ru

    2011-01-01

    Tryptophan dioxygenase (TDO) and Indoleamine 2,3 dioxygenase (IDO) are the only two heme-proteins that catalyze the oxidation reaction of tryptophan (Trp) to N-formylkynurenine (NFK). While human IDO (hIDO) is able to oxidize both L and D-Trp, human TDO (hTDO) displays a major specificity towards L-Trp. In this work we aim to interrogate the molecular basis for the substrate stereoselectivity of hTDO. Our previous molecular dynamics simulation studies of Xanthomonas campestris TDO (xcTDO) showed that an H-bond between T254 (T342 in hTDO) and the ammonium group of the substrate is present in the L-Trp-bound enzyme, but not in the D-Trp bound enzyme. The fact that this is the only notable structural alteration induced by the change in the stereo structure of the substrate prompted us to produce and characterize the T342A mutant of hTDO to evaluate the structural role of T342 in controlling the substrate stereoselectivity of the enzyme. The experimental results indicate that the mutation only slightly perturbs the global structural properties of the enzyme, but it totally abolishes the substrate stereoselectivity. Molecular Dynamics simulations of xcTDO show that T254 controls the substrate stereoselectivity of the enzyme by (i) modulating the H-bonding interaction between the NH3+ group and epoxide oxygen of the ferryl/indole 2,3-epoxide intermediate of the enzyme, and (ii) regulating the dynamics of two active site loops, loop250–260 and loop117–130, critical for substrate-binding. PMID:22082147

  1. Stereoselective silylcupration of conjugated alkynes in water at room temperature.

    PubMed

    Linstadt, Roscoe T H; Peterson, Carl A; Lippincott, Daniel J; Jette, Carina I; Lipshutz, Bruce H

    2014-04-14

    Micellar catalysis enables copper-catalyzed silylcupration of a variety of electron-deficient alkynes, thereby providing access to isomerically pure E- or Z-β-silyl-substituted carbonyl derivatives. These reactions take place in minutes, afford high yields and stereoselectivity, and are especially tolerant of functional groups present in the substrates. The aqueous reaction medium has been successfully recycled several times, and a substrate/catalyst ratio of 10,000:1 has been documented for this methodology.

  2. 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.

  3. 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.

  4. Stereoselective effects of MDMA on inhibition of monoamine uptake

    SciTech Connect

    Steele, T.D.; Nichols, D.E.; Yim, G.K.W.

    1986-03-05

    The R(-)-isomers of hallucinogenic phenylisopropylamines are most active, whereas the S(+)-enantiomers of amphetamine (AMPH) and methylenedioxymethamphetamine (MDMA) are more potent centrally. To determine if MDMA exhibits stereoselective effects at the biochemical level that resemble either those of amphetamine or the potent hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM), the ability of the isomers of MDMA, AMPH and DOM to inhibit uptake of radiolabelled monoamines into synaptosomes was measured. AMPH was more potent than MDMA in inhibiting uptake of /sup 3/H-norepinephrine (NE) into hypothalamic synaptosomes and /sup 3/H-dopamine (DA) into striatal synaptosomes. The S(+)-isomer was more active in each case. MDMA was more potent than AMPH in inhibiting uptake of /sup 3/H-serotonin (5-HT) into hippocampal synaptosomes and exhibited a high degree of stereoselectivity, in favor of the S(+)-isomer. DOM showed only minimal activity in inhibiting uptake of any monoamine (IC/sub 50/ > 10/sup -5/M). These results suggest that MDMA exhibits stereoselective effects similar to those of amphetamine on monoamine uptake inhibition, a parameter that is unrelated to the mechanism of action of the hallucinogen DOM.

  5. Stereoselective biotransformation of ketamine in equine liver and lung microsomes

    PubMed Central

    Schmitz, A.; Portier, C. J.; Thormann, W.; Theurillat, R.; Mevissen, M.

    2010-01-01

    Stereoselectivity has to be considered for pharmacodynamic and pharmacokinetic features of ketamine. Stereoselective biotransformation of ketamine was investigated in equine microsomes in vitro. Concentration curves were constructed over time, and enzyme activity was determined for different substrate concentrations using equine liver and lung microsomes. The concentrations of R/S-ketamine and R/S-norketamine were determined by enantioselective capillary electrophoresis. A two-phase model based on Hill kinetics was used to analyze the biotransformation of R/S-ketamine into R/S-norketamine and, in a second step, into R/S-downstream metabolites. In liver and lung microsomes, levels of R-ketamine exceeded those of S-ketamine at all time points and S-norketamine exceeded R-norketamine at time points below the maximum concentration. In liver and lung microsomes, significant differences in the enzyme velocity (Vmax) were observed between Sand R-norketamine formation and between Vmax of S-norketamine formation when S-ketamine was compared to S-ketamine of the racemate. Our investigations in microsomal reactions in vitro suggest that stereoselective ketamine biotransformation in horses occurs in the liver and the lung with a slower elimination of S-ketamine in the presence of R-ketamine. Scaling of the in vitro parameters to liver and lung organ clearances provided an excellent fit with previously published in vivo data and confirmed a lung first-pass effect. PMID:19000264

  6. Stereoselective Alkane Oxidation with meta-Chloroperoxybenzoic Acid (MCPBA) Catalyzed by Organometallic Cobalt Complexes.

    PubMed

    Shul'pin, Georgiy B; Loginov, Dmitriy A; Shul'pina, Lidia S; Ikonnikov, Nikolay S; Idrisov, Vladislav O; Vinogradov, Mikhail M; Osipov, Sergey N; Nelyubina, Yulia V; Tyubaeva, Polina M

    2016-11-22

    Cobalt pi-complexes, previously described in the literature and specially synthesized and characterized in this work, were used as catalysts in homogeneous oxidation of organic compounds with peroxides. These complexes contain pi-butadienyl and pi-cyclopentadienyl ligands: [(tetramethylcyclobutadiene)(benzene)cobalt] hexafluorophosphate, [(C₄Me₄)Co(C₆H₆)]PF₆ (1); diiodo(carbonyl)(pentamethylcyclopentadienyl)cobalt, Cp*Co(CO)I₂ (2); diiodo(carbonyl)(cyclopentadienyl)cobalt, CpCo(CO)I₂ (3); (tetramethylcyclobutadiene)(dicarbonyl)(iodo)cobalt, (C₄Me₄)Co(CO)₂I (4); [(tetramethylcyclobutadiene)(acetonitrile)(2,2'-bipyridyl)cobalt] hexafluorophosphate, [(C₄Me₄)Co(bipy)(MeCN)]PF₆ (5); bis[dicarbonyl(B-cyclohexylborole)]cobalt, [(C₄H₄BCy)Co(CO)₂]₂ (6); [(pentamethylcyclopentadienyl)(iodo)(1,10-phenanthroline)cobalt] hexafluorophosphate, [Cp*Co(phen)I]PF₆ (7); diiodo(cyclopentadienyl)cobalt, [CpCoI₂]₂ (8); [(cyclopentadienyl)(iodo)(2,2'-bipyridyl)cobalt] hexafluorophosphate, [CpCo(bipy)I]PF₆ (9); and [(pentamethylcyclopentadienyl)(iodo)(2,2'-bipyridyl)cobalt] hexafluorophosphate, [Cp*Co(bipy)I]PF₆ (10). Complexes 1 and 2 catalyze very efficient and stereoselective oxygenation of tertiary C-H bonds in isomeric dimethylcyclohexanes with MCBA: cyclohexanols are produced in 39 and 53% yields and with the trans/cis ratio (of isomers with mutual trans- or cis-configuration of two methyl groups) 0.05 and 0.06, respectively. Addition of nitric acid as co-catalyst dramatically enhances both the yield of oxygenates and stereoselectivity parameter. In contrast to compounds 1 and 2, complexes 9 and 10 turned out to be very poor catalysts (the yields of oxygenates in the reaction with cis-1,2-dimethylcyclohexane were only 5%-7% and trans/cis ratio 0.8 indicated that the oxidation is not stereoselective). The chromatograms of the reaction mixture obtained before and after reduction with PPh₃ are very similar, which testifies that alkyl

  7. Stereoselective Formation of Fully Substituted Ketone Enolates.

    PubMed

    Haimov, Elvira; Nairoukh, Zackaria; Shterenberg, Alexander; Berkovitz, Tiran; Jamison, Timothy F; Marek, Ilan

    2016-04-25

    The application of stereochemically defined acyclic fully substituted enolates of ketones to the enantioselective synthesis of quaternary carbon stereocenters would be highly valuable. Herein, we describe an approach leading to the formation of several new stereogenic centers through a combined metalation-addition of a carbonyl-carbamoyl transfer to reveal in situ stereodefined α,α-disubstituted enolates of ketone as a single stereoisomer. This approach could produce a series of aldol and Mannich products from enol carbamate with excellent diastereomeric ratios.

  8. Synthesis of (−)‐Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)‐Catalyzed Cycloisomerization

    PubMed Central

    Carreras, Javier; Kirillova, Mariia S.

    2016-01-01

    Abstract The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of a highly stereoselective gold(I)‐catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone. PMID:27119910

  9. Photosensitized [2 + 2] cycloaddition of N-acetylated cytosine affords stereoselective formation of cyclobutane pyrimidine dimer

    PubMed Central

    Yamamoto, Junpei; Nishiguchi, Kosuke; Manabe, Koichiro; Masutani, Chikahide; Hanaoka, Fumio; Iwai, Shigenori

    2011-01-01

    Photocycloaddition between two adjacent bases in DNA produces a cyclobutane pyrimidine dimer (CPD), which is one of the major UV-induced DNA lesions, with either the cis-syn or trans-syn structure. In this study, we investigated the photosensitized intramolecular cycloaddition of partially-protected thymidylyl-(3′→5′)-N4-acetyl-2′-deoxy-5-methylcytidine, to clarify the effect of the base modification on the cycloaddition reaction. The reaction resulted in the stereoselective formation of the trans-syn CPD, followed by hydrolysis of the acetylamino group. The same result was obtained for the photocycloaddition of thymidylyl-(3′→5′)-N4-acetyl-2′-deoxycytidine, whereas both the cis-syn and trans-syn CPDs were formed from thymidylyl-(3′→5′)-thymidine. Kinetic analyses revealed that the activation energy of the acid-catalyzed hydrolysis is comparable to that reported for the thymine-cytosine CPD. These findings provided a new strategy for the synthesis of oligonucleotides containing the trans-syn CPD. Using the synthesized oligonucleotide, translesion synthesis by human DNA polymerase η was analyzed. PMID:20880992

  10. A Stereoselective Route to Tetrahydrobenzoxazepines and Tetrahydrobenzodiazepines via Ring-Opening and Aza-Michael Addition of Activated Aziridines with 2-Hydroxyphenyl and 2-Aminophenyl Acrylates.

    PubMed

    Shahi, Chandan Kumar; Bhattacharyya, Aditya; Nanaji, Yerramsetti; Ghorai, Manas K

    2017-01-06

    A simple and efficient synthetic route to 2,3,4,5-tetrahydrobenzoxazepines and -benzodiazepines bearing easily functionalizable appendages has been developed by ring-opening of activated aziridines with 2-hydroxyphenyl acrylates and 2-aminophenyl acrylate, respectively, and subsequent intramolecular C-N bond formation through palladium-catalyzed aza-Michael reaction. The straightforward synthetic approach delivers the desired molecular scaffolds in high yields (up to 82%) with excellent stereoselectivity (ee up to 94%).

  11. Asymmetric synthesis and biological evaluations of (+)- and (-)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels.

    PubMed

    Yamamoto, Takashi; Ohno, Seiji; Niwa, Seiji; Tokumasu, Munetaka; Hagihara, Masako; Koganei, Hajime; Fujita, Shin-ichi; Takeda, Tomoko; Saitou, Yuki; Iwayama, Satoshi; Takahara, Akira; Iwata, Seinosuke; Shoji, Masataka

    2011-06-01

    An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using t-butyl ester of L-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (-)- and racemic isomers.

  12. Enantioselective cascade Michael addition/cyclization reactions of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles: efficient synthesis of functionalized polycyclic spirooxindoles.

    PubMed

    Tan, Fen; Lu, Liang-Qiu; Yang, Qing-Qing; Guo, Wei; Bian, Qiao; Chen, Jia-Rong; Xiao, Wen-Jing

    2014-03-17

    An unprecedented Zn(OTf)2-catalyzed asymmetric Michael addition/cyclization cascade of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles has been disclosed. This transformation provides an efficient access to various synthetically important polycyclic spirooxindoles in a highly stereoselective manner under mild conditions (72–99% yields, up to >95:5 d.r. and >99% ee). The reaction leads to the formation of three consecutive stereocenters, including 1,3-nonadjacent tetrasubstituted carbon stereocenters, in a single operation. A bifunctional activation model of the chiral Zn(OTf)2/bis(oxazoline) complex was proposed based on control experiments, wherein the ZnII moiety serves as a Lewis acid and the N atom of the free NH group acts as a Lewis base by a hydrogen-bonding interaction.

  13. Torsional Control of Stereoselectivities in Electrophilic Additions and Cycloadditions to Alkenes

    PubMed Central

    Wang, Hao; Houk, K. N.

    2013-01-01

    Torsional effects control the π-facial stereoselectivities of a variety of synthetically important organic reactions. This review surveys theoretical calculations that have led to the understanding of the influence of the torsional effects on several types of stereoselective organic reactions, especially electrophilic additions and cycloadditions to alkenes. PMID:24409340

  14. Ternary Cd(Se,Te) alloy semiconductors - Synthesis, material characterization, and high-efficiency photoelectrochemical cells

    NASA Astrophysics Data System (ADS)

    Levy-Clement, C.; Triboulet, R.; Rioux, J.; Etcheberry, A.; Licht, S.

    1985-12-01

    High-quality Cd(Se,Te) in two compositions was synthesized using the modified Bridgman technique. The Se-rich crystals had the hexagonal structure, while the Te-rich phase consisted of crystals with cubic packing. Their quality could be gauged from high-electron mobility and low resistivity, which suited the purpose of their synthesis, i.e., for high-efficiency photoelectrochemical cells. Photoelectrochemical etching was employed, which resulted in a heavily pitted surface with the density of the etch pits exceeding 10 to the 9th/sq cm. Quantum efficiency of the semiconductor/aqueous polysulfide interface increased considerably after photoetching. Solar-to-electrical conversion efficiencies in excess of 12 percent were obtained. Photoluminenscence spectrum was measured for the two crystals prior to and after photoetching. The emission maximum is near the calculated band gap. The decline in the luminescence intensity, after photoetching, is attributed to the corrugation of the surface and the reduced density of the donor state near the semiconductor surface, which increases the thickness of the space-charge layer (dead layer model).

  15. Self-templated synthesis of novel carbon nanoarchitectures for efficient electrocatalysis

    NASA Astrophysics Data System (ADS)

    Wu, Xi-Lin; Wen, Tao; Guo, Hong-Li; Liu, Shoujie; Wang, Xiangke; Xu, An-Wu; Mezger, Markus

    2016-06-01

    The cost-efficient large-scale production of novel carbon nanostructure with high performance is still a challenge, restricting their applications in catalysis. Herein, we present a low-cost one-pot and one-step approach for the synthesis of both N-doped graphene (NG) and N-doped carbon nanotubes (NCNTs) from self-templated organic nanoplates. By varying the FeCl3 concentration in the precursor, we can control the formation of graphene or CNTs. To the best of our knowledge, this is the first example for the controllable synthesis of graphene or CNTs by varying the precursors’ compositions. This provides a simple and cost-effective route for the large-scale production of both NG and NCNTs for applications in catalysis. By example, we show how these unique structured nanocarbons can be applied in electrocatalysis for oxygen reduction reaction (ORR). The obtained NG and NCNTs show excellent ORR activities with long-term stability under alkaline conditions. The unique porous nanostructure, abundant defects, homogeneous N-doping and high N-content in the NG and NCNTs can provide abundant active sites, leading to the excellent ORR performance. This research not only displayed a simple and cost-effective approach for the large-scale production of novel carbon nanoarchitectures, but also revealed the exceptional application potential of these nanocarbons for electrocatalysis.

  16. Bioreaction Engineering Leading to Efficient Synthesis of L-Glyceraldehyd-3-Phosphate.

    PubMed

    Molla, Getachew S; Kinfu, Birhanu M; Chow, Jennifer; Streit, Wolfgang; Wohlgemuth, Roland; Liese, Andreas

    2017-03-01

    Enantiopure L-glyceraldehyde-3-phosphate (L-GAP) is a useful building block in natural biological and synthetic processes. A biocatalytic process using glycerol kinase from Cellulomonas sp. (EC 2.7.1.30) catalyzed phosphorylation of L-glyceraldehyde (L-GA) by ATP is used for the synthesis of L-GAP. L-GAP has a half-life of 6.86 h under reaction conditions. The activity of this enzyme depends on the Mg(2+) to ATP molar ratio showing maximum activity at the optimum molar ratio of 0.7. A kinetic model is developed and validated showing a 2D correlation of 99.9% between experimental and numerical data matrices. The enzyme exhibits inhibition by ADP, AMP, methylglyoxal and Ca(2+) , but not by L-GAP and inorganic orthophosphate. Moreover, equal amount of Ca(2+) exerts a different degree of inhibition relative to the activity without the addition of Ca(2+) depending on the Mg(2+) to ATP molar ratio. If the Mg(2+) to ATP molar ratio is set to be at the optimum value or less, inorganic hexametaphosphate (PPi6) suppresses the enzyme activity; otherwise PPi6 enhances the enzyme activity. Based on reaction engineering parameters such as conversion, selectivity and specific productivity, evaluation of different reactor types reveals that batchwise operation via stirred-tank reactor is the most efficient process for the synthesis of L-GAP.

  17. Improving the time efficiency of the Fourier synthesis method for slice selection in magnetic resonance imaging.

    PubMed

    Tahayori, B; Khaneja, N; Johnston, L A; Farrell, P M; Mareels, I M Y

    2016-01-01

    The design of slice selective pulses for magnetic resonance imaging can be cast as an optimal control problem. The Fourier synthesis method is an existing approach to solve these optimal control problems. In this method the gradient field as well as the excitation field are switched rapidly and their amplitudes are calculated based on a Fourier series expansion. Here, we provide a novel insight into the Fourier synthesis method via representing the Bloch equation in spherical coordinates. Based on the spherical Bloch equation, we propose an alternative sequence of pulses that can be used for slice selection which is more time efficient compared to the original method. Simulation results demonstrate that while the performance of both methods is approximately the same, the required time for the proposed sequence of pulses is half of the original sequence of pulses. Furthermore, the slice selectivity of both sequences of pulses changes with radio frequency field inhomogeneities in a similar way. We also introduce a measure, referred to as gradient complexity, to compare the performance of both sequences of pulses. This measure indicates that for a desired level of uniformity in the excited slice, the gradient complexity for the proposed sequence of pulses is less than the original sequence.

  18. Design and Synthesis of Novel Block Copolymers for Efficient Opto-Electronic Applications

    NASA Technical Reports Server (NTRS)

    Sun, Sam-Shajing; Fan, Zhen; Wang, Yiqing; Taft, Charles; Haliburton, James; Maaref, Shahin

    2002-01-01

    It has been predicted that nano-phase separated block copolymer systems containing electron rich donor blocks and electron deficient acceptor blocks may facilitate the charge carrier separation and migration in organic photovoltaic devices due to improved morphology in comparison to polymer blend system. This paper presents preliminary data describing the design and synthesis of a novel Donor-Bridge-Acceptor (D-B-A) block copolymer system for potential high efficient organic optoelectronic applications. Specifically, the donor block contains an electron donating alkyloxy derivatized polyphenylenevinylene (PPV), the acceptor block contains an electron withdrawing alkyl-sulfone derivatized polyphenylenevinylene (PPV), and the bridge block contains an electronically neutral non-conjugated aliphatic hydrocarbon chain. The key synthetic strategy includes the synthesis of each individual block first, then couple the blocks together. While the donor block stabilizes and facilitates the transport of the holes, the acceptor block stabilizes and facilitates the transport of the electrons, the bridge block is designed to hinder the probability of electron-hole recombination. Thus, improved charge separation and stability are expected with this system. In addition, charge migration toward electrodes may also be facilitated due to the potential nano-phase separated and highly ordered block copolymer ultra-structure.

  19. Self-templated synthesis of novel carbon nanoarchitectures for efficient electrocatalysis.

    PubMed

    Wu, Xi-Lin; Wen, Tao; Guo, Hong-Li; Liu, Shoujie; Wang, Xiangke; Xu, An-Wu; Mezger, Markus

    2016-06-15

    The cost-efficient large-scale production of novel carbon nanostructure with high performance is still a challenge, restricting their applications in catalysis. Herein, we present a low-cost one-pot and one-step approach for the synthesis of both N-doped graphene (NG) and N-doped carbon nanotubes (NCNTs) from self-templated organic nanoplates. By varying the FeCl3 concentration in the precursor, we can control the formation of graphene or CNTs. To the best of our knowledge, this is the first example for the controllable synthesis of graphene or CNTs by varying the precursors' compositions. This provides a simple and cost-effective route for the large-scale production of both NG and NCNTs for applications in catalysis. By example, we show how these unique structured nanocarbons can be applied in electrocatalysis for oxygen reduction reaction (ORR). The obtained NG and NCNTs show excellent ORR activities with long-term stability under alkaline conditions. The unique porous nanostructure, abundant defects, homogeneous N-doping and high N-content in the NG and NCNTs can provide abundant active sites, leading to the excellent ORR performance. This research not only displayed a simple and cost-effective approach for the large-scale production of novel carbon nanoarchitectures, but also revealed the exceptional application potential of these nanocarbons for electrocatalysis.

  20. Self-templated synthesis of novel carbon nanoarchitectures for efficient electrocatalysis

    PubMed Central

    Wu, Xi-Lin; Wen, Tao; Guo, Hong-Li; Liu, Shoujie; Wang, Xiangke; Xu, An-Wu; Mezger, Markus

    2016-01-01

    The cost-efficient large-scale production of novel carbon nanostructure with high performance is still a challenge, restricting their applications in catalysis. Herein, we present a low-cost one-pot and one-step approach for the synthesis of both N-doped graphene (NG) and N-doped carbon nanotubes (NCNTs) from self-templated organic nanoplates. By varying the FeCl3 concentration in the precursor, we can control the formation of graphene or CNTs. To the best of our knowledge, this is the first example for the controllable synthesis of graphene or CNTs by varying the precursors’ compositions. This provides a simple and cost-effective route for the large-scale production of both NG and NCNTs for applications in catalysis. By example, we show how these unique structured nanocarbons can be applied in electrocatalysis for oxygen reduction reaction (ORR). The obtained NG and NCNTs show excellent ORR activities with long-term stability under alkaline conditions. The unique porous nanostructure, abundant defects, homogeneous N-doping and high N-content in the NG and NCNTs can provide abundant active sites, leading to the excellent ORR performance. This research not only displayed a simple and cost-effective approach for the large-scale production of novel carbon nanoarchitectures, but also revealed the exceptional application potential of these nanocarbons for electrocatalysis. PMID:27301537

  1. An efficient one-pot synthesis, characterization and antibacterial activity of novel chromeno-pyrimidine derivatives

    NASA Astrophysics Data System (ADS)

    Suresh, Lingala; Kumar, P. Sagar Vijay; Chandramouli, G. V. P.

    2017-04-01

    A simple and efficient one-pot three component, green protocol was established for the synthesis of chromenopyrano[2,3-d]pyrimidine derivatives starting from 3-amino-pyrano[2,3-c]chromene-2-carbonitrile, N,N-dimethylformamide dimethylacetal and aromatic amines in the presence of 1-butyl-3-methylimidazolium hydrogen sulphate[Bmim]HSO4 ionic liquid. The present procedure offers a domino reaction strategy, cleaner conversion, short reaction times and high yields. Among the screened derivatives, the compounds 4g and 4h were identified as lead molecules which established promising antimicrobial towards Gram-positive bacterial strains such as Staphylococcus aureus MTCC 96, Staphylococcus aureus MLS16 MTCC 2940 and Bacillus subtilis MTCC 121.

  2. ACCESS 3. Approximation concepts code for efficient structural synthesis: User's guide

    NASA Technical Reports Server (NTRS)

    Fleury, C.; Schmit, L. A., Jr.

    1980-01-01

    A user's guide is presented for ACCESS-3, a research oriented program which combines dual methods and a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and dual algorithms of mathematical programming are applied in the design optimization procedure. This program retains all of the ACCESS-2 capabilities and the data preparation formats are fully compatible. Four distinct optimizer options were added: interior point penalty function method (NEWSUMT); second order primal projection method (PRIMAL2); second order Newton-type dual method (DUAL2); and first order gradient projection-type dual method (DUAL1). A pure discrete and mixed continuous-discrete design variable capability, and zero order approximation of the stress constraints are also included.

  3. Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine.

    PubMed

    Chen, Weibin; Wu, Huifang; Bernard, Denzil; Metcalf, Matthew D; Deschamps, Jeffrey R; Flippen-Anderson, Judith L; MacKerell, Alexander D; Coop, Andrew

    2003-03-07

    Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.

  4. Different stereoselectivity in the reduction of pulegone by Mentha species.

    PubMed

    Fuchs, S; Beck, T; Mosandl, A

    2001-04-01

    Aqueous solutions of [2H]-labeled pulegone enantiomers were fed to Mentha spicata ssp. spicata L. and Mentha spicata ssp. crispata L. shoot tip and first leaf pair. After solid phase microextraction the essential oil was analysed with enantioselective multidimensional gas chromatography/mass spectrometry. Both Mentha spicata species were able to convert labelled (1R)- and (1S)-pulegone at the same rate into the corresponding menthone and isomenthone, indicating an unspecific process. The reduction of both pulegone enantiomers preferably led to the cis-stereoisomers. The observed stereoselectivity is completely different from those of pulegone reduction by Mentha x piperita L.

  5. Aromatic interactions as control elements in stereoselective organic reactions.

    PubMed

    Krenske, Elizabeth H; Houk, K N

    2013-04-16

    This Account describes how attractive interactions of aromatic rings with other groups can influence and control the stereoselectivity of many reactions. Recent developments in theory have improved the accuracy in the modeling of aromatic interactions. Quantum mechanical modeling can now provide insights into the roles of these interactions at a level of detail not previously accessible, both for ground-state species and for transition states of chemical reactions. In this Account, we show how transition-state modeling led to the discovery of the influence of aryl groups on the stereoselectivities of several types of organic reactions, including asymmetric dihydroxylations, transfer hydrogenations, hetero-Diels-Alder reactions, acyl transfers, and Claisen rearrangements. Our recent studies have also led to a novel mechanistic picture for two classes of (4 + 3) cycloadditions, both of which involve reactions of furans with oxyallyl intermediates. The first class of cycloadditions, developed by Hsung, features neutral oxyallyl intermediates that contain a chiral oxazolidinone auxiliary. Originally, it was thought that these cycloadditions relied on differential steric crowding of the two faces of a planar intermediate. Computations reveal a different picture and show that cycloaddition with furan takes place preferentially through the more crowded transition state: the furan adds on the same side as the Ph substituent of the oxazolidinone. The crowded transition state is stabilized by a CH-π interaction between furan and Ph worth approximately 2 kcal/mol. Attractive interactions with aromatic rings also control the stereoselectivity in a second class of (4+3) cycloadditions involving chiral alkoxy siloxyallyl cations. Alkoxy groups derived from chiral α-methylbenzyl alcohols favor crowded transition states, where a stabilizing CH-π interaction is present between the furan and the Ar group. The cationic cycloadditions are stepwise, while the Hsung cycloadditions

  6. Computing organic stereoselectivity - from concepts to quantitative calculations and predictions.

    PubMed

    Peng, Qian; Duarte, Fernanda; Paton, Robert S

    2016-11-07

    Advances in theory and processing power have established computation as a valuable interpretative and predictive tool in the discovery of new asymmetric catalysts. This tutorial review outlines the theory and practice of modeling stereoselective reactions. Recent examples illustrate how an understanding of the fundamental principles and the application of state-of-the-art computational methods may be used to gain mechanistic insight into organic and organometallic reactions. We highlight the emerging potential of this computational tool-box in providing meaningful predictions for the rational design of asymmetric catalysts. We present an accessible account of the field to encourage future synergy between computation and experiment.

  7. Investigation of a stereoselective co-mediated rearrangement reaction.

    PubMed

    Carbery, David R; Reignier, Serge; Miller, Neil D; Adams, Harry; Harrity, Joseph P A

    2003-05-30

    A stereocontrolled approach to alpha-alkyl beta-alkynyl cyclohexanones is reported through a Lewis acid mediated rearrangement reaction of enol ethers bearing an Co-alkyne moiety. The reaction proceeds with high levels of stereoselectivity in the presence of Ti- and B-Lewis acids to provide a range of alpha,beta-disubstituted cyclohexanones in high yield although the products are prone to epimerization at the alpha-position in the presence of the B-promoter system. The potential for an enantioselective variant of this process is outlined, and a rationale for the observed stereochemical trends and detailed structural analyses of the ketone products are described.

  8. Theoretical elucidation on the functional role of pyrrolidine-type ionic liquids in inducing stereoselectivity of the Michael addition of cyclohexanone with trans-β-nitrostyrene.

    PubMed

    Sun, Hui; Zhang, Dongju

    2011-03-01

    Density functional theory calculations have been carried out to elucidate the stereoselectivity of the Michael addition of cyclohexanone with trans-β-nitrostyrene, induced by a chiral ionic liquid (CIL) pyrrolidine-imidazolium bromide. By comparison of the C-C bond forming processes in the absence and presence of Br(-) anion, we found that intermolecular H-bonds between the imidazolium cation and the nitro group of trans-β-nitrostyrene and the steric hindrance of the imidazolium cation moiety on the Si-face of enamine dominate the stereoselectivity of the Michael addition. The presence of Br(-) anion obviously reduces the barrier by increasing the polarity of the C4=C5 bond of enamine. The theoretical results rationalize well the early experimental finding, and reveal a valuable clue for the further CIL design with high catalytic efficiency.

  9. Iodine catalyzed one-pot diamination of glycals with chloramine-T: a new approach to 2-amino-beta-glycosylamines for applications in N-glycopeptide synthesis.

    PubMed

    Kumar, Vipin; Ramesh, Namakkal G

    2006-12-21

    Iodine catalyzes a facile one-pot direct diamination of glycals with chloramine-T to afford stereoselectively 2-amino-beta-glycosylamine derivatives that serve as convenient precursors for the synthesis of N-linked glycopeptides.

  10. The Yeast Mitochondrial RNA Polymerase and Transcription Factor Complex Catalyzes Efficient Priming of DNA Synthesis on Single-stranded DNA.

    PubMed

    Ramachandran, Aparna; Nandakumar, Divya; Deshpande, Aishwarya P; Lucas, Thomas P; R-Bhojappa, Ramanagouda; Tang, Guo-Qing; Raney, Kevin; Yin, Y Whitney; Patel, Smita S

    2016-08-05

    Primases use single-stranded (ss) DNAs as templates to synthesize short oligoribonucleotide primers that initiate lagging strand DNA synthesis or reprime DNA synthesis after replication fork collapse, but the origin of this activity in the mitochondria remains unclear. Herein, we show that the Saccharomyces cerevisiae mitochondrial RNA polymerase (Rpo41) and its transcription factor (Mtf1) is an efficient primase that initiates DNA synthesis on ssDNA coated with the yeast mitochondrial ssDNA-binding protein, Rim1. Both Rpo41 and Rpo41-Mtf1 can synthesize short and long RNAs on ssDNA template and prime DNA synthesis by the yeast mitochondrial DNA polymerase Mip1. However, the ssDNA-binding protein Rim1 severely inhibits the RNA synthesis activity of Rpo41, but not the Rpo41-Mtf1 complex, which continues to prime DNA synthesis efficiently in the presence of Rim1. We show that RNAs as short as 10-12 nt serve as primers for DNA synthesis. Characterization of the RNA-DNA products shows that Rpo41 and Rpo41-Mtf1 have slightly different priming specificity. However, both prefer to initiate with ATP from short priming sequences such as 3'-TCC, TTC, and TTT, and the consensus sequence is 3'-Pu(Py)2-3 Based on our studies, we propose that Rpo41-Mtf1 is an attractive candidate for serving as the primase to initiate lagging strand DNA synthesis during normal replication and/or to restart stalled replication from downstream ssDNA.

  11. Micelle-Template Synthesis of Nitrogen-Doped Mesoporous Graphene as an Efficient Metal-Free Electrocatalyst for Hydrogen Production

    PubMed Central

    Huang, Xiaodan; Zhao, Yufei; Ao, Zhimin; Wang, Guoxiu

    2014-01-01

    Synthesis of mesoporous graphene materials by soft-template methods remains a great challenge, owing to the poor self-assembly capability of precursors and the severe agglomeration of graphene nanosheets. Herein, a micelle-template strategy to prepare porous graphene materials with controllable mesopores, high specific surface areas and large pore volumes is reported. By fine-tuning the synthesis parameters, the pore sizes of mesoporous graphene can be rationally controlled. Nitrogen heteroatom doping is found to remarkably render electrocatalytic properties towards hydrogen evolution reactions as a highly efficient metal-free catalyst. The synthesis strategy and the demonstration of highly efficient catalytic effect provide benchmarks for preparing well-defined mesoporous graphene materials for energy production applications. PMID:25523276

  12. Micelle-Template Synthesis of Nitrogen-Doped Mesoporous Graphene as an Efficient Metal-Free Electrocatalyst for Hydrogen Production

    NASA Astrophysics Data System (ADS)

    Huang, Xiaodan; Zhao, Yufei; Ao, Zhimin; Wang, Guoxiu

    2014-12-01

    Synthesis of mesoporous graphene materials by soft-template methods remains a great challenge, owing to the poor self-assembly capability of precursors and the severe agglomeration of graphene nanosheets. Herein, a micelle-template strategy to prepare porous graphene materials with controllable mesopores, high specific surface areas and large pore volumes is reported. By fine-tuning the synthesis parameters, the pore sizes of mesoporous graphene can be rationally controlled. Nitrogen heteroatom doping is found to remarkably render electrocatalytic properties towards hydrogen evolution reactions as a highly efficient metal-free catalyst. The synthesis strategy and the demonstration of highly efficient catalytic effect provide benchmarks for preparing well-defined mesoporous graphene materials for energy production applications.

  13. Highly efficient one-pot three-component synthesis of naphthopyran derivatives in water catalyzed by hydroxyapatite

    EPA Science Inventory

    An expeditious and efficient protocol for the synthesis of naphthopyrans has been developed that proceeds via one-pot three-component sequential reaction in water catalyzed by hydroxyapatite or sodium-modified-hydroxyapatite. The title compounds have been obtained in high yield a...

  14. Aqueous hydrotrope: an efficient and reusable medium for a green one-pot, diversity-oriented synthesis of quinazolinone derivatives.

    PubMed

    Patil, Amol; Barge, Madhuri; Rashinkar, Gajanan; Salunkhe, Rajashri

    2015-08-01

    A library of quinazolinones was prepared by the one-pot three-component reaction of isatoic anhydride, ammonium salts/amines, and various electrophiles using aqueous hydrotropic solution as an efficient, economical, reusable, and green medium giving good to excellent yields of products in very short time. The method offers a versatile way for the development of diversity-oriented synthesis of quinazolinones.

  15. AN EFFICIENT AND SIMPLE AQUEOUS N-HETEROCYCLIZATION OF ANILINE DERIVATIVES: MICROWAVE-ASSISTED SYNTHESIS OF N-ARYL AZACYCLOALKANES

    EPA Science Inventory

    An efficient and clean synthesis of N-aryl azacycloalkanes from alkyl dihalides and aniline derivatives has been achieved using microwave irradiation in an aqueous potassium carbonate medium. The phase separation can simplify the product isolation and reduce usage of vol...

  16. Highly efficient heterogeneous gold-catalyzed direct synthesis of tertiary and secondary amines from alcohols and urea.

    PubMed

    He, Lin; Qian, Yue; Ding, Ran-Sheng; Liu, Yong-Mei; He, He-Yong; Fan, Kang-Nian; Cao, Yong

    2012-04-01

    Urea, the white gold: The efficient synthesis of tertiary and secondary amines is achieved by heterogeneous gold-catalyzed direct amination of stoichiometric alcohols with urea in good to excellent yields. Via a hydrogen autotransfer pathway, the reactions of primary alcohols with urea give tertiary amines exclusively, while secondary alcohols selectively afford secondary amines.

  17. An efficient one-pot three-component synthesis of fused 1,4-dihydropyridines using HY-zeolite.

    PubMed

    Nikpassand, Mohammad; Mamaghani, Manouchehr; Tabatabaeian, Khalil

    2009-04-08

    A facile and convenient protocol was developed for the fast (2.5-3.5 h) and high yielding (70-90%) synthesis of fused 1,4-dihydropyridines from dimedone in the presence of HY-zeolite as an efficient recyclable heterogeneous catalyst.

  18. Origins of stereoselectivity in evolved ketoreductases.

    PubMed

    Noey, Elizabeth L; Tibrewal, Nidhi; Jiménez-Osés, Gonzalo; Osuna, Sílvia; Park, Jiyong; Bond, Carly M; Cascio, Duilio; Liang, Jack; Zhang, Xiyun; Huisman, Gjalt W; Tang, Yi; Houk, Kendall N

    2015-12-22

    Mutants of Lactobacillus kefir short-chain alcohol dehydrogenase, used here as ketoreductases (KREDs), enantioselectively reduce the pharmaceutically relevant substrates 3-thiacyclopentanone and 3-oxacyclopentanone. These substrates differ by only the heteroatom (S or O) in the ring, but the KRED mutants reduce them with different enantioselectivities. Kinetic studies show that these enzymes are more efficient with 3-thiacyclopentanone than with 3-oxacyclopentanone. X-ray crystal structures of apo- and NADP(+)-bound selected mutants show that the substrate-binding loop conformational preferences are modified by these mutations. Quantum mechanical calculations and molecular dynamics (MD) simulations are used to investigate the mechanism of reduction by the enzyme. We have developed an MD-based method for studying the diastereomeric transition state complexes and rationalize different enantiomeric ratios. This method, which probes the stability of the catalytic arrangement within the theozyme, shows a correlation between the relative fractions of catalytically competent poses for the enantiomeric reductions and the experimental enantiomeric ratio. Some mutations, such as A94F and Y190F, induce conformational changes in the active site that enlarge the small binding pocket, facilitating accommodation of the larger S atom in this region and enhancing S-selectivity with 3-thiacyclopentanone. In contrast, in the E145S mutant and the final variant evolved for large-scale production of the intermediate for the antibiotic sulopenem, R-selectivity is promoted by shrinking the small binding pocket, thereby destabilizing the pro-S orientation.

  19. Origins of stereoselectivity in evolved ketoreductases

    PubMed Central

    Noey, Elizabeth L.; Tibrewal, Nidhi; Jiménez-Osés, Gonzalo; Osuna, Sílvia; Park, Jiyong; Bond, Carly M.; Cascio, Duilio; Liang, Jack; Zhang, Xiyun; Huisman, Gjalt W.; Tang, Yi; Houk, Kendall N.

    2015-01-01

    Mutants of Lactobacillus kefir short-chain alcohol dehydrogenase, used here as ketoreductases (KREDs), enantioselectively reduce the pharmaceutically relevant substrates 3-thiacyclopentanone and 3-oxacyclopentanone. These substrates differ by only the heteroatom (S or O) in the ring, but the KRED mutants reduce them with different enantioselectivities. Kinetic studies show that these enzymes are more efficient with 3-thiacyclopentanone than with 3-oxacyclopentanone. X-ray crystal structures of apo- and NADP+-bound selected mutants show that the substrate-binding loop conformational preferences are modified by these mutations. Quantum mechanical calculations and molecular dynamics (MD) simulations are used to investigate the mechanism of reduction by the enzyme. We have developed an MD-based method for studying the diastereomeric transition state complexes and rationalize different enantiomeric ratios. This method, which probes the stability of the catalytic arrangement within the theozyme, shows a correlation between the relative fractions of catalytically competent poses for the enantiomeric reductions and the experimental enantiomeric ratio. Some mutations, such as A94F and Y190F, induce conformational changes in the active site that enlarge the small binding pocket, facilitating accommodation of the larger S atom in this region and enhancing S-selectivity with 3-thiacyclopentanone. In contrast, in the E145S mutant and the final variant evolved for large-scale production of the intermediate for the antibiotic sulopenem, R-selectivity is promoted by shrinking the small binding pocket, thereby destabilizing the pro-S orientation. PMID:26644568

  20. Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives☆

    PubMed Central

    Orden, Alejandro A.; Schrittwieser, Joerg H.; Resch, Verena; Mutti, Francesco G.; Kroutil, Wolfgang

    2013-01-01

    A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the diastereoselective reduction of a Bischler–Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomer. PMID:24503964

  1. Efficient synthesis and evaluation of bis-pyridinium/bis-quinolinium metallosalophens as antibiotic and antitumor candidates

    NASA Astrophysics Data System (ADS)

    Elshaarawy, Reda F. M.; Eldeen, Ibrahim M.; Hassan, Eman M.

    2017-01-01

    Inspired with the pharmacological diversity of salophens and in our endeavor to explore a new strategy which may conflict the invasion of drug resistance, we report herein efficient synthetic routes for the synthesis of new RO-salophen(Cl), pyridinium/quinolinium-based salophens (3a-e) and metallosalophens (4a-j). These new architectures have been structurally characterized by elemental and spectral analysis as well pharmacologically evaluated for their in vitro antimicrobial, against a common panel of pathogenic bacterial and fungal strains, and anticancer activities against human colon carcinoma (HCT-116) cell lines. Antimicrobial assay results revealed that all tested compounds exhibited moderate to superb broad-spectrum efficacy in comparison to the standard antibiotic with a preferential ability to perform as a fungicides than to act as bactericides. Noteworthy, VO(II)-salophens are more effective in reduction HCT-116 cell viability than Cu(II)-salophens. For example, VO(II)-salophen3 (4f) (IC50 = 2.13 μg/mL) was ca. 10-fold more efficient than Cu(II)-salophen3 (4e) (IC50 = 20.30 μg/mL).

  2. Efficient Catalytic Activity BiFeO3 Nanoparticles Prepared by Novel Microwave-Assisted Synthesis.

    PubMed

    Zou, Jing; Gong, Wanyun; Ma, Jinai; Li, Lu; Jiang, Jizhou

    2015-02-01

    A novel microwave-assisted sol-gel method was applied to the synthesis of the single-phase perovskite bismuth ferrite nanoparticles (BFO NPs) with the mean diameter ca. 73.7 nm. The morphology was characterized by scanning electron microscope (SEM). The X-ray diffraction (XRD) revealed the rhombohedral phase with R3c space group. The weak ferromagnetic behavior at room temperature was affirmed by the vibrating sample magnetometer (VSM). According to the UV-vis diffuse reflectance spectrum (UV-DSR), the band gap energy of BFO NPs was determined to be 2.18 eV. The electrochemical activity was evaluated by BFO NPs-chitosan-glassy carbon electrode (BFO-CS-GCE) sensor for detection of p-nitrophenol contaminants. The material showed an efficient oxidation catalytic activity by degrading methylene blue (MB). It was found that the degradation efficiency of 10 mg L-1 MB at pH 6.0 was above 90.9% after ultrasound- and microwave-combined-assisted (US-MW) irradiation for 15 min with BFO NPs as catalyst and H202 as oxidant. A possible reaction mechanism of degradation of MB was also proposed.

  3. Efficient Rhodium-Catalyzed Multicomponent Reaction for the Synthesis of Novel Propargylamines.

    PubMed

    Rubio-Pérez, Laura; Iglesias, Manuel; Munárriz, Julen; Polo, Victor; Pérez-Torrente, Jesús J; Oro, Luis A

    2015-12-01

    [{Rh(μ-Cl)(H)2 (IPr)}2 ] (IPr = 1,3-bis-(2,6-diisopropylphenyl)imidazole-2-ylidene) was found to be an efficient catalyst for the synthesis of novel propargylamines by a one-pot three-component reaction between primary arylamines, aliphatic aldehydes, and triisopropylsilylacetylene. This methodology offers an efficient synthetic pathway for the preparation of secondary propargylamines derived from aliphatic aldehydes. The reactivity of [{Rh(μ-Cl)(H)2 (IPr)}2 ] with amines and aldehydes was studied, leading to the identification of complexes [RhCl(CO)IPr(MesNH2 )] (MesNH2 = 2,4,6-trimethylaniline) and [RhCl(CO)2 IPr]. The latter shows a very low catalytic activity while the former brought about reaction rates similar to those obtained with [{Rh(μ-Cl)(H)2 (IPr)}2 ]. Besides, complex [RhCl(CO)IPr(MesNH2 )] reacts with an excess of amine and aldehyde to give [RhCl(CO)IPr{MesNCHCH2 CH(CH3 )2 }], which was postulated as the active species. A mechanism that clarifies the scarcely studied catalytic cycle of A3 -coupling reactions is proposed based on reactivity studies and DFT calculations.

  4. A Facile Synthesis of Nitrogen-Doped Highly Porous Carbon Nanoplatelets: Efficient Catalysts for Oxygen Electroreduction.

    PubMed

    Zhang, Yaqing; Zhang, Xianlei; Ma, Xiuxiu; Guo, Wenhui; Wang, Chunchi; Asefa, Tewodros; He, Xingquan

    2017-02-27

    The oxygen reduction reaction (ORR) is of great importance for various renewable energy conversion technologies such as fuel cells and metal-air batteries. Heteroatom-doped carbon nanomaterials have proven to be robust metal-free electrocatalysts for ORR in the above-mentioned energy devices. Herein, we demonstrate the synthesis of novel highly porous N-doped carbon nanoplatelets (N-HPCNPs) derived from oatmeal (or a biological material) and we show the materials' high-efficiency as electrocatalyst for ORR. The obtained N-HPCNPs hybrid materials exhibit superior electrocatalytic activities towards ORR, besides excellent stability and good methanol tolerance in both basic and acidic electrolytes. The unique nanoarchitectures with rich micropores and mesopores, as well as the high surface area-to-volume ratios, present in the materials significantly increase the density of accessible catalytically active sites in them and facilitate the transport of electrons and electrolyte within the materials. Consequently, the N-HPCNPs catalysts hold a great potential to serve as low-cost and highly efficient cathode materials in direct methanol fuel cells (DMFCs).

  5. Efficient Synthesis of Peptide and Protein Functionalized Pyrrole-Imidazole Polyamides Using Native Chemical Ligation

    PubMed Central

    Janssen, Brian M. G.; van Ommeren, Sven P. F. I.; Merkx, Maarten

    2015-01-01

    The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py–Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py–Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py–Im polyamides. The effect of Py–Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py–Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py–Im-polyamide conjugates. The practical use of protein-Py–Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established. PMID:26053396

  6. A Facile Synthesis of Nitrogen-Doped Highly Porous Carbon Nanoplatelets: Efficient Catalysts for Oxygen Electroreduction

    NASA Astrophysics Data System (ADS)

    Zhang, Yaqing; Zhang, Xianlei; Ma, Xiuxiu; Guo, Wenhui; Wang, Chunchi; Asefa, Tewodros; He, Xingquan

    2017-02-01

    The oxygen reduction reaction (ORR) is of great importance for various renewable energy conversion technologies such as fuel cells and metal-air batteries. Heteroatom-doped carbon nanomaterials have proven to be robust metal-free electrocatalysts for ORR in the above-mentioned energy devices. Herein, we demonstrate the synthesis of novel highly porous N-doped carbon nanoplatelets (N-HPCNPs) derived from oatmeal (or a biological material) and we show the materials’ high-efficiency as electrocatalyst for ORR. The obtained N-HPCNPs hybrid materials exhibit superior electrocatalytic activities towards ORR, besides excellent stability and good methanol tolerance in both basic and acidic electrolytes. The unique nanoarchitectures with rich micropores and mesopores, as well as the high surface area-to-volume ratios, present in the materials significantly increase the density of accessible catalytically active sites in them and facilitate the transport of electrons and electrolyte within the materials. Consequently, the N-HPCNPs catalysts hold a great potential to serve as low-cost and highly efficient cathode materials in direct methanol fuel cells (DMFCs).

  7. Nonlinear inverse synthesis for high spectral efficiency transmission in optical fibers.

    PubMed

    Le, Son Thai; Prilepsky, Jaroslaw E; Turitsyn, Sergei K

    2014-11-03

    In linear communication channels, spectral components (modes) defined by the Fourier transform of the signal propagate without interactions with each other. In certain nonlinear channels, such as the one modelled by the classical nonlinear Schrödinger equation, there are nonlinear modes (nonlinear signal spectrum) that also propagate without interacting with each other and without corresponding nonlinear cross talk, effectively, in a linear manner. Here, we describe in a constructive way how to introduce such nonlinear modes for a given input signal. We investigate the performance of the nonlinear inverse synthesis (NIS) method, in which the information is encoded directly onto the continuous part of the nonlinear signal spectrum. This transmission technique, combined with the appropriate distributed Raman amplification, can provide an effective eigenvalue division multiplexing with high spectral efficiency, thanks to highly suppressed channel cross talk. The proposed NIS approach can be integrated with any modulation formats. Here, we demonstrate numerically the feasibility of merging the NIS technique in a burst mode with high spectral efficiency methods, such as orthogonal frequency division multiplexing and Nyquist pulse shaping with advanced modulation formats (e.g., QPSK, 16QAM, and 64QAM), showing a performance improvement up to 4.5 dB, which is comparable to results achievable with multi-step per span digital back propagation.

  8. Efficient Synthesis of Peptide and Protein Functionalized Pyrrole-Imidazole Polyamides Using Native Chemical Ligation.

    PubMed

    Janssen, Brian M G; van Ommeren, Sven P F I; Merkx, Maarten

    2015-06-04

    The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py-Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py-Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py-Im polyamides. The effect of Py-Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py-Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py-Im-polyamide conjugates. The practical use of protein-Py-Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established.

  9. A Facile Synthesis of Nitrogen-Doped Highly Porous Carbon Nanoplatelets: Efficient Catalysts for Oxygen Electroreduction

    PubMed Central

    Zhang, Yaqing; Zhang, Xianlei; Ma, Xiuxiu; Guo, Wenhui; Wang, Chunchi; Asefa, Tewodros; He, Xingquan

    2017-01-01

    The oxygen reduction reaction (ORR) is of great importance for various renewable energy conversion technologies such as fuel cells and metal-air batteries. Heteroatom-doped carbon nanomaterials have proven to be robust metal-free electrocatalysts for ORR in the above-mentioned energy devices. Herein, we demonstrate the synthesis of novel highly porous N-doped carbon nanoplatelets (N-HPCNPs) derived from oatmeal (or a biological material) and we show the materials’ high-efficiency as electrocatalyst for ORR. The obtained N-HPCNPs hybrid materials exhibit superior electrocatalytic activities towards ORR, besides excellent stability and good methanol tolerance in both basic and acidic electrolytes. The unique nanoarchitectures with rich micropores and mesopores, as well as the high surface area-to-volume ratios, present in the materials significantly increase the density of accessible catalytically active sites in them and facilitate the transport of electrons and electrolyte within the materials. Consequently, the N-HPCNPs catalysts hold a great potential to serve as low-cost and highly efficient cathode materials in direct methanol fuel cells (DMFCs). PMID:28240234

  10. Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms.

    PubMed

    Bagnall, John; Malia, Louis; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2013-10-01

    Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds.

  11. Opposite Stereoselectivities of Dirigent Proteins in Arabidopsis and Schizandra Species*

    PubMed Central

    Kim, Kye-Won; Moinuddin, Syed G. A.; Atwell, Kathleen M.; Costa, Michael A.; Davin, Laurence B.; Lewis, Norman G.

    2012-01-01

    How stereoselective monolignol-derived phenoxy radical-radical coupling reactions are differentially biochemically orchestrated in planta, whereby for example they afford (+)- and (−)-pinoresinols, respectively, is both a fascinating mechanistic and evolutionary question. In earlier work, biochemical control of (+)-pinoresinol formation had been established to be engendered by a (+)-pinoresinol-forming dirigent protein in Forsythia intermedia, whereas the presence of a (−)-pinoresinol-forming dirigent protein was indirectly deduced based on the enantiospecificity of downstream pinoresinol reductases (AtPrRs) in Arabidopsis thaliana root tissue. In this study of 16 putative dirigent protein homologs in Arabidopsis, AtDIR6, AtDIR10, and AtDIR13 were established to be root-specific using a β-glucuronidase reporter gene strategy. Of these three, in vitro analyses established that only recombinant AtDIR6 was a (−)-pinoresinol-forming dirigent protein, whose physiological role was further confirmed using overexpression and RNAi strategies in vivo. Interestingly, its closest homolog, AtDIR5, was also established to be a (−)-pinoresinol-forming dirigent protein based on in vitro biochemical analyses. Both of these were compared in terms of properties with a (+)-pinoresinol-forming dirigent protein from Schizandra chinensis. In this context, sequence analyses, site-directed mutagenesis, and region swapping resulted in identification of putative substrate binding sites/regions and candidate residues controlling distinct stereoselectivities of coupling modes. PMID:22854967

  12. Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

    NASA Technical Reports Server (NTRS)

    Profy, A. T.; Usher, D. A.

    1984-01-01

    The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

  13. Palladium(0)-Catalyzed Heteroarylation of 2- and 3-Indolylzinc Derivatives. An Efficient General Method for the Preparation of (2-Pyridyl)indoles and Their Application to Indole Alkaloid Synthesis.

    PubMed

    Amat, Mercedes; Hadida, Sabine; Pshenichnyi, Grigorii; Bosch, Joan

    1997-05-16

    Palladium(0)-catalyzed coupling of (1-(benzenesulfonyl)-2-indolyl)zinc chloride (1) and (1-(tert-butyldimethylsilyl)-3-indolyl)zinc chloride (6) with diversely substituted (alkyl, methoxy, methoxycarbonyl, nitro, hydroxy) 2-halopyridines gives the corresponding 2- and 3-(2-pyridyl)indoles [4 and 7 (or 8), respectively] in excellent yields. A series of other 3-(heteroaryl)indoles (pyrazinyl, furyl, thienyl, indolyl) have been similarly prepared from 6. The potential of some of these (2-pyridyl)indoles in alkaloid synthesis is demonstrated. Thus, from 2-(2-pyridyl)indole 4b, a new synthetic entry to the indolo[2,3-a]quinolizidine system, involving stereoselective hydrogenation of the pyridine ring with subsequent electrophilic cyclization upon the indole 3-position from an appropriately N(b)-substituted 2-(2-piperidyl)indole, is reported. For this purpose, Pummerer cyclizations have been extensively studied. Whereas the indole-unprotected sulfoxide 17 gives the corresponding indoloquinolizidine 19 in low yield and mainly undergoes an abnormal Pummerer cyclization that ultimately leads to sulfide 18, the N(a)-protected sulfoxides 24a and 24b afford the respective indoloquinolizidines 25a,b in 70% yield. On the other hand, the conversion of 3-(2-pyridyl)indole 8k into tetracyclic ketone 35 by stereoselective hydrogenation, followed by cyclization of the resulting all-cis-3-(2-piperidyl)indole 34, represents a formal synthesis of Strychnos alkaloids with the strychnan skeletal type (tubifoline, tubifolidine, 19,20-dihydroakuammicine). A similar conversion of 8j into nordasycarpidone constitutes a formal synthesis of the alkaloids of the uleine group. Reduction of nordasycarpidone leads to tetracycle 37, an advanced intermediate in a previous synthesis of tubotaiwine, a Strychnos alkaloid with the aspidospermatan skeletal type. Finally, piperidylindole 34 was transformed into tetracycle 41, an ABDE substructure of akuammiline alkaloids, by a sequence involving the

  14. Development of efficient, small particle size luminescent oxides using combustion synthesis

    NASA Astrophysics Data System (ADS)

    Shea, Lauren Elizabeth

    Luminescent materials (phosphors) find application in cathode-ray tubes (CRTs), medical and industrial equipment monitors, fluorescent lamps, xerography, and many types of flat panel displays. Many commercially available phosphors were optimized in the 1960s for high voltage (>10 kV) CRT applications. Recently, a great deal of emphasis has been placed on the development and improvement of phosphors for flat panel displays that operate at low voltages (<5 kV). In addition to high efficiency at low voltages, these displays demand high resolution phosphor screens which can only be realized using phosphors with smaller particle size (<3 mum). Conventional methods of preparing phosphors (e.g., high temperature solid-state reaction) cannot easily produce a homogeneous product with uniform, small particle size. In this work, a novel ceramic synthesis technique, combustion synthesis, was used for the first time to produce submicron-sized oxide phosphors more efficiently for use in flat panel displays. This technique exploits the exothermic redox reaction of metal nitrates (oxidizers) with an organic fuel (reducing agent). Typical fuels include urea (CHsb4Nsb2O), carbohydrazide (CHsb6Nsb4O), or glycine (Csb2Hsb5NOsb2). Resulting powders were well-crystallized, with a large surface area and small particle size. Phosphor powders were exposed to photoluminescence excitation by high energy (254 nm, E = 4.88 eV) and low energy photons (365 nm, E = 3.4 eV and 435 nm, E = 2.85 eV) and cathodoluminescence excitation by a low-voltage (100-1000 V) electron beam. Photoluminescence (PL) techniques resulted in the measurement of spectral energy distribution and relative intensities. Phosphor efficiencies in lumens per watt (lm/W) were obtained by low-voltage cathodoluminescence measurements. The effects of processing parameters such as type of fuel, fuel to oxidizer ratio, and heating rate were studied. The combustion process was optimized based on these processing parameters in order

  15. An Efficient Synthesis Strategy for Metal-Organic Frameworks: Dry-Gel Synthesis of MOF-74 Framework with High Yield and Improved Performance

    NASA Astrophysics Data System (ADS)

    Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; McGrail, B. Peter; Motkuri, Radha Kishan

    2016-06-01

    Vapor-assisted dry-gel synthesis of the metal-organic framework-74 (MOF-74) structure, specifically Ni-MOF-74 produced from synthetic precursors using an organic-water hybrid solvent system, showed a very high yield (>90% with respect to 2,5-dihydroxyterepthalic acid) and enhanced performance. The Ni-MOF-74 obtained showed improved sorption characteristics towards CO2 and the refrigerant fluorocarbon dichlorodifluoromethane. Unlike conventional synthesis, which takes 72 hours using the tetrahydrofuran-water system, this kinetic study showed that Ni-MOF-74 forms within 12 hours under dry-gel conditions with similar performance characteristics, and exhibits its best performance characteristics even after 24 hours of heating. In the dry-gel conversion method, the physical separation of the solvent and precursor mixture allows for recycling of the solvent. We demonstrated efficient solvent recycling (up to three times) that resulted in significant cost benefits. The scaled-up manufacturing cost of Ni-MOF-74 synthesized via our dry-gel method is 45% of conventional synthesis cost. Thus, for bulk production of the MOFs, the proposed vapor-assisted, dry-gel method is efficient, simple, and inexpensive when compared to the conventional synthesis method.

  16. An Efficient Synthesis Strategy for Metal-Organic Frameworks: Dry-Gel Synthesis of MOF-74 Framework with High Yield and Improved Performance

    PubMed Central

    Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; McGrail, B. Peter; Motkuri, Radha Kishan

    2016-01-01

    Vapor-assisted dry-gel synthesis of the metal-organic framework-74 (MOF-74) structure, specifically Ni-MOF-74 produced from synthetic precursors using an organic-water hybrid solvent system, showed a very high yield (>90% with respect to 2,5-dihydroxyterepthalic acid) and enhanced performance. The Ni-MOF-74 obtained showed improved sorption characteristics towards CO2 and the refrigerant fluorocarbon dichlorodifluoromethane. Unlike conventional synthesis, which takes 72 hours using the tetrahydrofuran-water system, this kinetic study showed that Ni-MOF-74 forms within 12 hours under dry-gel conditions with similar performance characteristics, and exhibits its best performance characteristics even after 24 hours of heating. In the dry-gel conversion method, the physical separation of the solvent and precursor mixture allows for recycling of the solvent. We demonstrated efficient solvent recycling (up to three times) that resulted in significant cost benefits. The scaled-up manufacturing cost of Ni-MOF-74 synthesized via our dry-gel method is 45% of conventional synthesis cost. Thus, for bulk production of the MOFs, the proposed vapor-assisted, dry-gel method is efficient, simple, and inexpensive when compared to the conventional synthesis method. PMID:27306598

  17. An Efficient Synthesis Strategy for Metal-Organic Frameworks: Dry-Gel Synthesis of MOF-74 Framework with High Yield and Improved Performance.

    PubMed

    Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; McGrail, B Peter; Motkuri, Radha Kishan

    2016-06-16

    Vapor-assisted dry-gel synthesis of the metal-organic framework-74 (MOF-74) structure, specifically Ni-MOF-74 produced from synthetic precursors using an organic-water hybrid solvent system, showed a very high yield (>90% with respect to 2,5-dihydroxyterepthalic acid) and enhanced performance. The Ni-MOF-74 obtained showed improved sorption characteristics towards CO2 and the refrigerant fluorocarbon dichlorodifluoromethane. Unlike conventional synthesis, which takes 72 hours using the tetrahydrofuran-water system, this kinetic study showed that Ni-MOF-74 forms within 12 hours under dry-gel conditions with similar performance characteristics, and exhibits its best performance characteristics even after 24 hours of heating. In the dry-gel conversion method, the physical separation of the solvent and precursor mixture allows for recycling of the solvent. We demonstrated efficient solvent recycling (up to three times) that resulted in significant cost benefits. The scaled-up manufacturing cost of Ni-MOF-74 synthesized via our dry-gel method is 45% of conventional synthesis cost. Thus, for bulk production of the MOFs, the proposed vapor-assisted, dry-gel method is efficient, simple, and inexpensive when compared to the conventional synthesis method.

  18. Tuning the Synthesis of Manganese Oxides Nanoparticles for Efficient Oxidation of Benzyl Alcohol

    NASA Astrophysics Data System (ADS)

    Fei, Jingyuan; Sun, Lixian; Zhou, Cuifeng; Ling, Huajuan; Yan, Feng; Zhong, Xia; Lu, Yuxiang; Shi, Jeffrey; Huang, Jun; Liu, Zongwen

    2017-01-01

    The liquid phase oxidation of benzyl alcohol is an important reaction for generating benzaldehyde and benzoic acid that are largely required in the perfumery and pharmaceutical industries. The current production systems suffer from either low conversion or over oxidation. From the viewpoint of economy efficiency and environmental demand, we are aiming to develop new high-performance and cost-effective catalysts based on manganese oxides that can allow the green aerobic oxidation of benzyl alcohol under mild conditions. It was found that the composition of the precursors has significant influence on the structure formation and surface property of the manganese oxide nanoparticles. In addition, the crystallinity of the resulting manganese nanoparticles was gradually improved upon increasing the calcination temperature; however, the specific surface area decreased obviously due to pore structure damage at higher calcination temperature. The sample calcined at the optimal temperature of 600 °C from the precursors without porogen was a Mn3O4-rich material with a small amount of Mn2O3, which could generate a significant amount of {O}_2- species on the surface that contributed to the high catalytic activity in the oxidation. Adding porogen with precursors during the synthesis, the obtained catalysts were mainly Mn2O3 crystalline, which showed relatively low activity in the oxidation. All prepared samples showed high selectivity for benzaldehyde and benzoic acid. The obtained catalysts are comparable to the commercial OMS-2 catalyst. The synthesis-structure-catalysis interaction has been addressed, which will help for the design of new high-performance selective oxidation catalysts.

  19. Tuning the Synthesis of Manganese Oxides Nanoparticles for Efficient Oxidation of Benzyl Alcohol.

    PubMed

    Fei, Jingyuan; Sun, Lixian; Zhou, Cuifeng; Ling, Huajuan; Yan, Feng; Zhong, Xia; Lu, Yuxiang; Shi, Jeffrey; Huang, Jun; Liu, Zongwen

    2017-12-01

    The liquid phase oxidation of benzyl alcohol is an important reaction for generating benzaldehyde and benzoic acid that are largely required in the perfumery and pharmaceutical industries. The current production systems suffer from either low conversion or over oxidation. From the viewpoint of economy efficiency and environmental demand, we are aiming to develop new high-performance and cost-effective catalysts based on manganese oxides that can allow the green aerobic oxidation of benzyl alcohol under mild conditions. It was found that the composition of the precursors has significant influence on the structure formation and surface property of the manganese oxide nanoparticles. In addition, the crystallinity of the resulting manganese nanoparticles was gradually improved upon increasing the calcination temperature; however, the specific surface area decreased obviously due to pore structure damage at higher calcination temperature. The sample calcined at the optimal temperature of 600 °C from the precursors without porogen was a Mn3O4-rich material with a small amount of Mn2O3, which could generate a significant amount of [Formula: see text] species on the surface that contributed to the high catalytic activity in the oxidation. Adding porogen with precursors during the synthesis, the obtained catalysts were mainly Mn2O3 crystalline, which showed relatively low activity in the oxidation. All prepared samples showed high selectivity for benzaldehyde and benzoic acid. The obtained catalysts are comparable to the commercial OMS-2 catalyst. The synthesis-structure-catalysis interaction has been addressed, which will help for the design of new high-performance selective oxidation catalysts.

  20. 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.

  1. Evolution of Catalytic Stereoselective Olefin Metathesis: From Ancillary Transformation to Purveyor of Stereochemical Identity

    PubMed Central

    2015-01-01

    There have been numerous significant advances in catalytic olefin metathesis (OM) during the past two decades. Such progress has transformed this important set of reactions to strategically pivotal processes that generate stereochemical identity while delivering molecules that cannot be easily prepared by alternative routes. In this Perspective, an analysis of the origin of the inception of bidentate benzylidene ligands for Ru-based OM catalysts is first presented. This is followed by an overview of the intellectual basis that culminated in the development of Mo-based diolates and stereogenic-at-Ru complexes for enantioselective OM. The principles accrued from the study of the latter Ru carbenes and Mo alkylidenes and utilized in the design of stereogenic-at-Mo, -W, and -Ru species applicable to enantioselective and Z-selective OM are then discussed. The influence of the recently introduced catalytic OM protocols on the design of synthesis routes leading to complex organic molecules is probed. The impact of a better understanding of the mechanistic nuances of OM toward the discovery of stereoselective catalysts is reviewed as well. PMID:24720633

  2. Efficient cascade synthesis of ampicillin from penicillin G potassium salt using wild and mutant penicillin G acylase from Alcaligenes faecalis.

    PubMed

    Deng, Senwen; Ma, Xiaoqiang; Su, Erzheng; Wei, Dongzhi

    2016-02-10

    To avoid isolation and purification of the intermediate 6-aminopenicillanic acid (6-APA), a two-enzyme two-step cascade synthesis of ampicillin from penicillin G was established. In purely aqueous medium, penicillin G hydrolysis and ampicillin synthesis were catalyzed by immobilized wild-type and mutagenized penicillin G acylases from Alcaligenes faecalis (Af PGA), respectively (Fig. 1). The βF24 G mutant Af PGA (the 24th Phenylalanine of the β-subunit was replaced by Glycine) was employed for its superior performance in enzymatic synthesis of ampicillin. By optimizing the reaction conditions, including enzyme loading, temperature, initial pH and D-PGME/6-APA ratio, the conversion of the second step of ampicillin synthesis reached approximately 90% in 240 min and less than 1.7 mole D-PGME were required to produce 1 mole ampicillin. Overall, in a 285 min continuous two-step procedure, an ampicillin yield of 87% was achieved, demonstrating the possibility of improving the cascade synthesis of ampicillin by mutagenized PGA, providing an economically efficient and environmentally benign procedure for semi-synthetic penicillins antibiotics synthesis.

  3. Can oriented-attachment be an efficient growth mechanism for the synthesis of 1D nanocrystals via atomic layer deposition?

    NASA Astrophysics Data System (ADS)

    Wen, Kechun; He, Weidong

    2015-09-01

    One-dimensional (1D) nanocrystals, such as nanorods and nanowires, have received extensive attention in the nanomaterials field due to their large surface areas and 1D confined transport properties. Oriented attachment (OA) is now recognized as a major growth mechanism for efficiently synthesizing 1D nanocrystals. Recently, atomic layer deposition (ALD) has been modified to be a powerful vapor-phase technique with which to synthesize 1D OA nanorods/nanowires with high efficiency and quality by increasing the temperature and purging time. In this invited mini-review, we look into the advantages of OA and high-temperature ALD, and investigate the potential of employing the OA growth mechanism for the synthesis of 1D nanocrystals via modified ALD, aiming to provide guidance to researchers in the fields of both OA and ALD for efficient synthesis of 1D nanocrystals.

  4. Assessing translational efficiency by a reporter protein co-expressed in a cell-free synthesis system.

    PubMed

    Park, Yu Jin; Lee, Kyung-Ho; Kim, Dong-Myung

    2017-02-01

    We demonstrate the use of a cell-free protein synthesis system as a convenient tool for assessing the relative translational efficiencies of genes. When sfGFP was used as a common reporter gene and co-expressed with a series of target genes, the intensities of sfGFP fluorescence from the co-expression reactions were highly correlated with the individual expression levels of the co-expressed genes. The relative translational efficiencies of genes estimated by this method were reproducible when the same genes were expressed in transformed Escherichia coli, suggesting that this method could be used as a universal tool for prognostic assessment of translational efficiency.

  5. Synthesis of pterostilbene by Julie Olefination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A simple, stereoselective route for the synthesis of the biologically active compounds trans-pterostilbene and tetramethoxy stilbene from the readily available starting materials 3,5-dimethoxy benzyl alcohol and 4-hydroxy benzaldehyde was developed using Julia olefination as a key reaction....

  6. Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS

    PubMed Central

    Masters, Andrea R.; McCoy, Michael; Jones, David R.; Desta, Zeruesenay

    2016-01-01

    Bupropion metabolites formed via oxidation and reduction exhibit pharmacological activity, but little is known regarding their stereoselective disposition. A novel stereoselective liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantify enantiomers of bupropion, 4-hydroxybupropion, and erythro- and threo-dihydrobupropion. Liquid-liquid extraction was implemented to extract all analytes from 50µL human plasma. Acetaminophen (APAP) was used as an internal standard. The analytes were separated on a Lux 3µ Cellulose-3 250×4.6 mm column by methanol: acetonitrile: ammonium bicarbonate: ammonium hydroxide gradient elution and monitored using an ABSciex 5500 QTRAP triple-quadrupole mass spectrometer equipped with electrospray ionization probe in positive mode. Extraction efficiency for all analytes was ≥70%. The stability at a single non-extracted concentration for over 48 hours at ambient temperature resulted in less than 9.8% variability for all analytes. The limit of quantification (LOQ) for enantiomers of bupropion and 4-hydroxybupropion was 0.3ng/mL, while the LOQ for enantiomers of erythro- and threo-hydrobupropion was 0.15ng/mL. The intra-day precision and accuracy estimates for enantiomers of bupropion and its metabolites ranged from 3.4% to 15.4% and from 80.6% to 97.8%, respectively, while the inter-day precision and accuracy ranged from 6.1% to 19.9% and from 88.5% to 99.9%, respectively. The current method was successfully implemented to determine the stereoselective pharmacokinetics of bupropion and its metabolites in a healthy volunteer administered a single 100 mg oral dose of racemic bupropion. This novel, accurate, and precise HPLC-MS/MS method should enhance further research into bupropion stereoselective metabolism and drug interactions. PMID:26946423

  7. Total Synthesis and Structural Revision of Vannusals A and B. Synthesis of the True Structures of Vannusals A and B

    PubMed Central

    Ortiz, Adrian; Zhang, Hongjun; Guella, Graziano

    2010-01-01

    Having determined, through total synthesis, that the originally assigned structure of vannusals A and B were incorrect, we set out to uncover the identity of the true structures of these novel marine natural products. Our search was based on intelligence gathered by NMR spectroscopy and chemical synthesis and took us through the total synthesis of eight diastereomeric vannusal B structures [2, d-2, 3, d-3, 4, d-4, 5, and d-5, Figure 1]. The true structures of vannusals A and B were finally determined to be d-5 and d-1, respectively. Their total synthesis was based on a highly convergent and efficient strategy that involved fragments vinyl iodide (−)-6 and aldehyde (±)-94, and featured a stereoselective lithium-mediated coupling reaction and a samarium-induced cyclization process that forged the final ring of the carbon framework. The synthetic strategies and technologies developed in these investigations expand the scope of chemical synthesis and render these compounds readily available for biological evaluation, while the NMR spectroscopic insights gained should prove useful in future structural determination endeavors. PMID:20443558

  8. Aromatic Interactions as Control Elements in Stereoselective Organic Reactions

    PubMed Central

    2012-01-01

    Conspectus This Account describes how attractive interaction of aromatic rings with other groups can influence and control the stereoselectivity of many reactions. Recent developments in theory have led to improved accuracy in the modeling of aromatic interactions. Quantum mechanical modeling can now provide insights into the roles of these interactions at a level of detail not previously accessible, both for ground-state species and for transition states of chemical reactions. In this Account, we show how transition-state modeling led to the discovery of the influence of aryl groups on the stereoselectivities of several types of organic reactions. These reaction types include asymmetric dihydroxylations, transfer hydrogenations, hetero-Diels–Alder reactions, acyl transfers, and Claisen rearrangements. Our recent studies have led to a novel mechanistic picture for two classes of (4+3) cycloadditions, both of which involve reactions of furans with oxyallyl intermediates. The first class of cycloadditions, developed by Hsung, features neutral oxyallyls containing a chiral oxazolidinone auxiliary. Originally, these cycloadditions were thought rely on differential steric crowding of the two faces of a planar intermediate. Computations reveal a different picture and show that cycloadditions with furan takes place preferentially through the more crowded transition state, with furan adding on the same side as the oxazolidinone’s Ph substituent. The crowded transition state is stabilized by a CH–π interaction between furan and Ph, worth about 2.0 kcal/mol. Stereocontrol in a second class of (4+3) cycloadditions, involving chiral alkoxy siloxyallyl cations, also is controlled by attractive interactions with aromatic rings. Alkoxy groups derived from chiral α-methylbenzyl alcohols are found to favor crowded transition states, where a CH–π interaction is again present between furan and Ar. The cationic cycloadditions are stepwise, while the Hsung cycloadditions are

  9. Efficient synthesis of tension modulation in strings and membranes based on energy estimation.

    PubMed

    Avanzini, Federico; Marogna, Riccardo; Bank, Balázs

    2012-01-01

    String and membrane vibrations cannot be considered as linear above a certain amplitude due to the variation in string or membrane tension. A relevant special case is when the tension is spatially constant and varies in time only in dependence of the overall string length or membrane surface. The most apparent perceptual effect of this tension modulation phenomenon is the exponential decay of pitch in time. Pitch glides due to tension modulation are an important timbral characteristic of several musical instruments, including the electric guitar and tom-tom drum, and many ethnic instruments. This paper presents a unified formulation to the tension modulation problem for one-dimensional (1-D) (string) and two-dimensional (2-D) (membrane) cases. In addition, it shows that the short-time average of the tension variation, which is responsible for pitch glides, is approximately proportional to the system energy. This proportionality allows the efficient physics-based sound synthesis of pitch glides. The proposed models require only slightly more computational resources than linear models as opposed to earlier tension-modulated models of higher complexity.

  10. Phase and composition controllable synthesis of cobalt manganese spinel nanoparticles towards efficient oxygen electrocatalysis

    PubMed Central

    Li, Chun; Han, Xiaopeng; Cheng, Fangyi; Hu, Yuxiang; Chen, Chengcheng; Chen, Jun

    2015-01-01

    Spinel-type oxides are technologically important in many fields, including electronics, magnetism, catalysis and electrochemical energy storage and conversion. Typically, these materials are prepared by conventional ceramic routes that are energy consuming and offer limited control over shape and size. Moreover, for mixed-metal oxide spinels (for example, CoxMn3−xO4), the crystallographic phase sensitively correlates with the metal ratio, posing great challenges to synthesize active product with simultaneously tuned phase and composition. Here we report a general synthesis of ultrasmall cobalt manganese spinels with tailored structural symmetry and composition through facile solution-based oxidation–precipitation and insertion–crystallization process at modest condition. As an example application, the nanocrystalline spinels catalyse the oxygen reduction/evolution reactions, showing phase and composition co-dependent performance. Furthermore, the mild synthetic strategy allows the formation of homogeneous and strongly coupled spinel/carbon nanocomposites, which exhibit comparable activity but superior durability to Pt/C and serve as efficient catalysts to build rechargeable Zn–air and Li–air batteries. PMID:26040417

  11. Facile and Efficient Synthesis of Carbosiloxane Dendrimers via Orthogonal Click Chemistry Between Thiol and Ene.

    PubMed

    Zhang, Zhida; Feng, Shengyu; Zhang, Jie

    2016-02-01

    A combination of a thiol-Michael addition reaction and a free radical mediated thiol-ene reaction is employed as a facile and efficient approach to carbosiloxane dendrimer synthesis. For the first time, carbosiloxane dendrimers are constructed rapidly by an orthogonal click strategy without protection/deprotection procedures. The chemoselectivity of these two thiol-ene click reactions leads to a design of a new monomer containing both electron-deficient carbon-carbon double bonds and unconjugated carbon-carbon double bonds. Siloxane bonds are introduced as the linker between these two kinds of carbon-carbon double bonds. Starting from a bifunctional thiol core, the dendrimers are constructed by iterative thiol-ene click reactions under different but both mild reaction conditions. After simple purification steps the fifth dendrimer with 54 peripheral functional groups is obtained with an excellent overall yield in a single day. Furthermore, a strong blue glow is observed when the dendrimer is excited by a UV lamp.

  12. Green synthesis of copper nanoparticles for the efficient removal (degradation) of dye from aqueous phase.

    PubMed

    Sinha, Tanur; Ahmaruzzaman, M

    2015-12-01

    The present work reports the utilization of a common household waste material (fish scales of Labeo rohita) for the synthesis of copper nanoparticles. The method so developed was found to be green, environment-friendly, and economic. The fish scale extracts were acting as a stabilizing and reducing agents. This method avoids the use of external reducing and stabilizing agents, templates, and solvents. The compositional abundance of gelatin may be envisaged for the effective reductive as well as stabilizing potency. The mechanisms for the formation of nanoparticles have also been presented. The synthesized copper nanoparticles formed were predominantly spherical in nature with an average size of nanoparticles in the range of 25-37 nm. The copper nanoparticles showed characteristic Bragg's reflection planes of fcc which was supported by both selected area electron diffraction and X-ray diffraction pattern and showed surface plasmon resonance at 580 nm. Moreover, the energy dispersive spectroscopy pattern also revealed the presence of only elemental copper in the copper nanoparticles. The prepared nanoparticles were used for the remediation of a carcinogenic and noxious textile dye, Methylene blue, from aqueous solution. Approximately, 96 % degradation of Methylene blue dye was observed within 135 min using copper nanoparticles. The probable mechanism for the degradation of the dye has been presented, and the degraded intermediates have been identified using the liquid chromatography-mass spectroscopy technique. The high efficiency of nanoparticles as photocatalysts has opened a promising application for the removal of hazardous dye from industrial effluents contributing indirectly to environmental cleanup process.

  13. Efficient, chemoselective synthesis of immunomicelles using single-domain antibodies with a C-terminal thioester

    PubMed Central

    Reulen, Sanne WA; van Baal, Ingrid; Raats, Jos MH; Merkx, Maarten

    2009-01-01

    Background Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL). However, current methods to generate antibody fragments with C-terminal thioesters require cumbersome refolding procedures, effectively preventing application of NCL for antibody-mediated targeting and molecular imaging. Results Targeting to the periplasm of E. coli allowed efficient production of correctly-folded single-domain antibody (sdAb)-intein fusions proteins. On column purification and 2-mercapthoethanesulfonic acid (MESNA)-induced cleavage yielded single-domain antibodies with a reactive C-terminal MESNA thioester in good yields. These thioester-functionalized single-domain antibodies allowed synthesis of immunomicelles via native chemical ligation in a single step. Conclusion A novel procedure was developed to obtain soluble, well-folded single-domain antibodies with reactive C-terminal thioesters in good yields. These proteins are promising building blocks for the chemoselective functionalization via NCL of a broad range of nanoparticle scaffolds, including micelles, liposomes and dendrimers. PMID:19619333

  14. Phase and composition controllable synthesis of cobalt manganese spinel nanoparticles towards efficient oxygen electrocatalysis

    NASA Astrophysics Data System (ADS)

    Li, Chun; Han, Xiaopeng; Cheng, Fangyi; Hu, Yuxiang; Chen, Chengcheng; Chen, Jun

    2015-06-01

    Spinel-type oxides are technologically important in many fields, including electronics, magnetism, catalysis and electrochemical energy storage and conversion. Typically, these materials are prepared by conventional ceramic routes that are energy consuming and offer limited control over shape and size. Moreover, for mixed-metal oxide spinels (for example, CoxMn3-xO4), the crystallographic phase sensitively correlates with the metal ratio, posing great challenges to synthesize active product with simultaneously tuned phase and composition. Here we report a general synthesis of ultrasmall cobalt manganese spinels with tailored structural symmetry and composition through facile solution-based oxidation-precipitation and insertion-crystallization process at modest condition. As an example application, the nanocrystalline spinels catalyse the oxygen reduction/evolution reactions, showing phase and composition co-dependent performance. Furthermore, the mild synthetic strategy allows the formation of homogeneous and strongly coupled spinel/carbon nanocomposites, which exhibit comparable activity but superior durability to Pt/C and serve as efficient catalysts to build rechargeable Zn-air and Li-air batteries.

  15. Towards efficient chemical synthesis via engineering enzyme catalysis in biomimetic nanoreactors.

    PubMed

    Liu, Jia; Yang, Qihua; Li, Can

    2015-09-18

    Biocatalysis with immobilized enzymes as catalysts holds enormous promise in developing more efficient and sustainable processes for the synthesis of fine chemicals, chiral pharmaceuticals and biomass feedstocks. Despite the appealing potentials, nowadays the industrial-scale application of biocatalysts is still quite modest in comparison with that of traditional chemical catalysts. A critical issue is that the catalytic performance of enzymes, the sophisticated and vulnerable catalytic machineries, strongly depends on their intracellular working environment; however the working circumstances provided by the support matrix are radically different from those in cells. This often leads to various adverse consequences on enzyme conformation and dynamic properties, consequently decreasing the overall performance of immobilized enzymes with regard to their activity, selectivity and stability. Engineering enzyme catalysis in support nanopores by mimicking the physiological milieu of enzymes in vivo and investigating how the interior microenvironment of nanopores imposes an influence on enzyme behaviors in vitro are of paramount significance to modify and improve the catalytic functions of immobilized enzymes. In this feature article, we have summarized the recent advances in mimicking the working environment and working patterns of intracellular enzymes in nanopores of mesoporous silica-based supports. Especially, we have demonstrated that incorporation of polymers into silica nanopores could be a valuable approach to create the biomimetic microenvironment for enzymes in the immobilized state.

  16. Simple and efficient synthesis of 2-[(18)F]fluoroethyl triflate for high yield (18)fluoroethylation.

    PubMed

    Peters, Tanja; Vogg, Andreas; Oppel, Iris M; Schmaljohann, Jörn

    2014-12-01

    The [(18)F]fluoroethyl moiety has been widely utilized in the synthesis of (18)F-labelled compounds. The aim of this work was the reliable synthesis of [(18)F]FEtOTf with a novel strategy to increase the reactivity of the commonly used [(18)F]FEB and [(18)F]FEtOTos. [(18)F]FEtOTf and the intermediate [(18)F]FEtOH were synthesized in high RCY (78% and 85%, respectively) and purified by SPE. The high potency of [(18)F]FEtOTf was shown by the efficient alkylation of the deactivated nucleophile aniline under mild conditions, as well as by the synthesis of [(18)F]FEC.

  17. Effect of total mixed ration composition on fermentation and efficiency of ruminal microbial crude protein synthesis in vitro.

    PubMed

    Boguhn, J; Kluth, H; Rodehutscord, M

    2006-05-01

    The goal of this study was to identify dietary factors that affect fermentation and efficiency of microbial crude protein (CP(M)) synthesis in the rumen in vitro. We used 16 total mixed, dairy cow rations with known digestibilities that varied in ingredient composition and nutrient content. Each ration was incubated in a Rusitec (n = 3) for 15 d, and fermentation of different fractions was assessed. Observed extents of fermentation in 24 h were 35 to 47% for organic matter, 25 to 60% for crude protein, 3 to 28% for neutral detergent fiber, and 31 to 45% for gross energy. Organic matter fermentation depended on the content of crude protein and neutral detergent fiber in the ration. We studied net synthesis of CP(M) using an 15N dilution technique and found that 7 d of continuous 15N application are needed to achieve an 15N enrichment plateau in the N of isolated microbes in this type of study. The efficiency of CP(M) synthesis was 141 to 286 g/kg of fermented organic matter or 4.9 to 11.1 g/MJ of metabolizable energy, and these ranges agree with those found in the literature. Multiple regressions to predict the efficiency of CP(M) synthesis by diet data showed that crude protein was the only dietary chemical fraction that had a significant effect. Fat content and the inclusion rate of corn silage in the ration also tended to improve efficiency. We suggest that microbial need for preformed amino acids may explain the crude protein effect. A large part of the variation in efficiency of microbial activity still remains unexplained.

  18. Determination of the quantitative stereoselectivity fingerprint of lipases during hydrolysis of a prochiral triacylglycerol.

    PubMed

    Mitchell, David Alexander; Rodriguez, Jorge A; Carrière, Frederic; Krieger, Nadia

    2008-06-01

    We propose a method for characterizing quantitatively the stereoselectivity of lipases during hydrolysis of triacylglycerols. Although it is of general applicability, we demonstrate it specifically for sn-1,3-regiospecific lipases. In this case the method generates a "stereoselectivity fingerprint" that consists of ratios of the specificity constants for the various reactions that produce and consume the 1,2-sn- and 2,3-sn-diacylglycerols. We use the method to determine the stereoselectivity fingerprint of several lipases during the hydrolysis of the prochiral substrate triolein. Our method opens up the possibility of correlating quantitative fingerprints with structural information, in the quest to elucidate the mechanisms underlying the stereoselectivity of lipases.

  19. Reaction of allenyl esters with sodium azide: an efficient synthesis of e-vinyl azides and polysubstituted pyrroles.

    PubMed

    Huang, Xian; Shen, Ruwei; Zhang, Tiexin

    2007-02-16

    The nucleophilic addition of sodium azide to 1,2-allenyl esters can generate vinyl azides in excellent yields with excellent regio- and stereoselectivities. Moreover, pyrroles are synthesized using 1-allyllic 1,2-allenyl esters as substrates in t-BuOH at 65 degrees C. The sequential reaction for pyrroles is developed on the basis of a novel domino process involving nucleophilic addition, cycloaddition, denitrogenation, and aromatization.

  20. An Efficient Solution-Phase Synthesis of 4,5,7-Trisubstituted Pyrrolo[3,2-d]pyrimidines

    PubMed Central

    Zhang, Weihe; Liu, Jing; Stashko, Michael A.; Wang, Xiaodong

    2013-01-01

    We have developed an efficient and robust route to synthesize 4,5,7-trisubstituted pyrrolo[3,2-d]pyrimidines as potent kinase inhibitors. This solution-phase synthesis features a SNAr substitution reaction, cross-coupling reaction, one-pot reduction/reductive amination and N-alkylation reaction. These reactions occur rapidly with high yields and have broad substrate scopes. A variety of groups can be selectively introduced into the N5 and C7 positions of 4,5,7-trisubstituted pyrrolopyrimidines at a late stage of the synthesis, thereby providing a highly efficient approach to explore the structure-activity relationships of pyrrolopyrimidine derivatives. Four synthetic analogs have been profiled against a panel of 48 kinases and a new and selective FLT3 inhibitor 9 is identified. PMID:23181516

  1. Ultrasonic irradiation assisted efficient regioselective synthesis of CF3-containing pyrazoles catalyzed by Cu(OTf)2/Et3N

    PubMed Central

    2013-01-01

    Background Most of the known approaches to the synthesis of CF3-containing organic compounds suffer from serious drawbacks. For example the starting materials required for these methods are rather difficult to obtain, or they are fairly toxic and inconvenient to work with and methods for direct fluorination and trifluoromethylation do not always allow the introduction of the CF3-group at the required position of a molecule. Results An efficient and attractive regioselective synthesis of a series of novel pyrazoles containing the trifluromethyl moiety was achieved using Cu(OTf)2/Et3N as an efficient catalytic system under ultrasonic irradiation. Conclusions Cu(OTf)2/Et3N catalyst showed a great advantage over all the investigated catalysts, and the ultrasonic irradiation method offered high yields of pyrazoles in short reaction time compared with classical conditions. gHMBC spectra of the product were used to rationalize the observed regioselectivity. PMID:23764261

  2. Time- and energy-efficient solution combustion synthesis of binary metal tungstate nanoparticles with enhanced photocatalytic activity.

    PubMed

    Thomas, Abegayl; Janáky, Csaba; Samu, Gergely F; Huda, Muhammad N; Sarker, Pranab; Liu, J Ping; van Nguyen, Vuong; Wang, Evelyn H; Schug, Kevin A; Rajeshwar, Krishnan

    2015-05-22

    In the search for stable and efficient photocatalysts beyond TiO2 , the tungsten-based oxide semiconductors silver tungstate (Ag2 WO4 ), copper tungstate (CuWO4 ), and zinc tungstate (ZnWO4 ) were prepared using solution combustion synthesis (SCS). The tungsten precursor's influence on the product was of particular relevance to this study, and the most significant effects are highlighted. Each sample's photocatalytic activity towards methyl orange degradation was studied and benchmarked against their respective commercial oxide sample obtained by solid-state ceramic synthesis. Based on the results herein, we conclude that SCS is a time- and energy-efficient method to synthesize crystalline binary tungstate nanomaterials even without additional excessive heat treatment. As many of these photocatalysts possess excellent photocatalytic activity, the discussed synthetic strategy may open sustainable materials chemistry avenues to solar energy conversion and environmental remediation.

  3. Efficient Synthesis of Poly(hydroxyethyl Methacrylate)-b-Poly(dimethylaminoethyl Methacrylate) Block Copolymer by Atom Transfer Radical Polymerization.

    NASA Astrophysics Data System (ADS)

    Tang, Wei; Loo, Yueh-Lin

    2009-03-01

    Polymers containing hydroxyethyl methacrylate (HEMA) and dimethylaminoethyl methacrylate (DMAEMA) have found wide applications in areas such as bioseparation, tissue engineering and controlled drug delivery. The controlled synthesis of block copolymers of PDMAEMA-b-PHEMA from PDMAEMA macroinitiator by atom transfer radical polymerization (ATRP), however, has not been successful due to the loss of chain end functionality during polymerization. We report an ATRP system that affords efficient chain extension from PDMAEMA to HEMA using Cu(0)/1,1,4,7,10,10-hexamethyltriethylenetetramine as the catalyst, 2-chloropropionitrile as the initiator in methanol at room temperature. A clear peak shift in the gel permeation chromatography trace towards shorter elution times indicates chain growth on HEMA addition. The chain end functionalities of PDMAEMA are thus retained and can be used to efficiently initiate chain extension reaction of HEMA. This new synthetic route opens new possibilities for the synthesis of pH- and temperature-responsive systems containing DMAEMA.

  4. Synthesis of Hydroxylated Bicyclic Amino Acids from l-Tyrosine: Octahydro-1H-indole Carboxylates

    PubMed Central

    Pierce, Joshua G.; Kasi, Dhanalakshmi; Fushimi, Makoto; Cuzzupe, Anthony; Wipf, Peter

    2009-01-01

    A stereoselective approach to polyhydroxylated l-Choi derivatives has been developed. The oxidative cyclization of l-tyrosine was optimized to avoid partial racemization and to allow a more efficient scale-up. PMID:18767800

  5. Gold nanoparticles supported on titanium dioxide: an efficient catalyst for highly selective synthesis of benzoxazoles and benzimidazoles.

    PubMed

    Tang, Lin; Guo, Xuefeng; Yang, Yu; Zha, Zhenggen; Wang, Zhiyong

    2014-06-11

    A highly efficient and selective reaction for the synthesis of 2-substituted benzoxazoles and benzimidazoles catalyzed by Au/TiO2 has been developed via two hydrogen-transfer processes. This reaction has a good tolerance to air and water, a wide substrate scope, and represents a new avenue for practical C-N and C-O bond formation. More importantly, no additional additives, oxidants and reductants are required for the reaction and the catalyst can be recovered and reused readily.

  6. A new and efficient synthesis of 6-O-methylscutellarein, the major metabolite of the natural medicine scutellarin.

    PubMed

    Zhang, Wei; Dong, Ze-Xi; Gu, Ting; Li, Nian-Guang; Zhang, Peng-Xuan; Wu, Wen-Yu; Yu, Shao-Peng; Tang, Yu-Ping; Yang, Jian-Ping; Shi, Zhi-Hao

    2015-06-02

    In this paper, a new and efficient synthesis of 6-O-methylscutellarein (3), the major metabolite of the natural medicine scutellarin, is reported. Two hydroxyl groups at C-4' and C-7 in 2 were selectively protected by chloromethyl methyl ether after the reaction conditions were optimized, then 6-O-methyl-scutellarein (3) was produced in high yield after methylation of the hydroxyl group at C-6 and subsequent deprotection of the two methyl ether groups.

  7. An efficient total synthesis of a potent anti-inflammatory agent, benzocamphorin F, and its anti-inflammatory activity.

    PubMed

    Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung

    2012-01-01

    A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo.

  8. An Efficient Total Synthesis of a Potent Anti-Inflammatory Agent, Benzocamphorin F, and Its Anti-Inflammatory Activity

    PubMed Central

    Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung

    2012-01-01

    A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo. PMID:22949872

  9. Clean and efficient synthesis of O-silylcarbamates and ureas in supercritical carbon dioxide.

    PubMed

    Fuchter, Matthew J; Smith, Catherine J; Tsang, Melanie W S; Boyer, Alistair; Saubern, Simon; Ryan, John H; Holmes, Andrew B

    2008-05-14

    The synthesis of a family of O-silylcarbamates from the corresponding silylamines has been achieved simply by heating the silylamine in supercritical carbon dioxide (scCO2), and these O-silylcarbamates have been shown to be effective precursors for the synthesis of a range of symmetrical and unsymmetrical ureas.

  10. Efficient continuous synthesis of high purity deep eutectic solvents by twin screw extrusion.

    PubMed

    Crawford, D E; Wright, L A; James, S L; Abbott, A P

    2016-03-18

    Mechanochemical synthesis has been applied to the rapid synthesis of Deep Eutectic Solvents (DESs), including Reline 200 (choline chloride : urea, 1 : 2), in a continuous flow methodology by Twin Screw Extrusion (TSE). This gave products in higher purity and with Space Time Yields (STYs), four orders of magnitude greater than for batch methods.

  11. Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

    PubMed Central

    Bretzke, Sebastian; Scheeff, Stephan; Vollmeyer, Felicitas; Eberhagen, Friederike; Rominger, Frank

    2016-01-01

    Summary The design, development and application of an efficient procedure for the concise synthesis of the 1,3-syn- and anti-tetrahydropyrimidine cores of manzacidins are reported. The intramolecular allylic substitution reaction of a readily available joint urea-type substrate enables the facile preparation of both diastereomers in high yields. The practical application of this approach is demonstrated in the efficient and modular preparation of the authentic heterocyclic cores of manzacidins, structurally unique bromopyrrole alkaloids of marine origin. Additional features of this route include the stereoselective generation of the central amine core with an appending quaternary center by an asymmetric addition of a Grignard reagent to a chiral tert-butanesulfinyl ketimine following an optimized Ellman protocol and a cross-metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. PMID:27340499

  12. Facile and controlled synthesis of aligned WO3 nanorods and nanosheets as an efficient photocatalyst material

    NASA Astrophysics Data System (ADS)

    Ahmed, Bilal; Kumar, Sumeet; Ojha, Animesh K.; Donfack, P.; Materny, A.

    2017-03-01

    In this work, we have performed a facile and controlled synthesis of WO3 nanorods and sheets in different crystal phases (triclinic, orthorhombic and monoclinic) of WO3 using the sol-gel method. The detailed structures of the synthesized materials were examined by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and Raman spectroscopy measurements. The shapes and crystal phases of the WO3 nanostructures were found to be highly dependent on the calcination temperature. The variation in crystalline phases and shapes is modified the electronic structure of the samples, which causes a variation in the value of optical band gap. The value of the Raman line intensity ratio I264/I320 has been successfully used to identify the structural transition from the triclinic to the orthorhombic phase of WO3. The PL spectra of the synthesized products excited at wavelengths 380, 400, and 420 nm exhibit intense emission peaks that cover the complete visible range (blue-green-red). The emission peaks at 460 and 486 nm were caused by the near band-edge and band to band transition, respectively. The peaks in spectral range 500-600 nm might be originated from the presence of oxygen vacancies lying within the energy band gap. The synthesized WO3 nanostructures showed improved photocatalytic activity for the photodegradation of MB dye. The enhanced photocatalytic activity of WO3 nanosheets compared to WO3 nanorods for photodegradation of methylene blue (MB) dye could be due to the shape of the nanostructured WO3. The sheet type of structure provides more active surface for the interaction of dye molecules compared to the rods, which results in a more efficient degradation of the dye molecules.

  13. Rapid (∼10 min) synthesis of single-crystalline, nanorice TiO2 mesoparticles with a high photovoltaic efficiency of above 8%.

    PubMed

    Parmar, K P S; Ramasamy, Easwaramoorthi; Lee, Jinwoo; Lee, Jae Sung

    2011-08-14

    A novel rapid (∼10 min) microwave-hydrothermal synthesis is demonstrated for nanorice TiO(2) mesoparticles as an anode of a dye-sensitized solar cell with an excellent photovoltaic efficiency of above 8%.

  14. Transition metal-catalyzed efficient and green transformations of P(O)-H compounds to functional organophosphorus compounds.

    PubMed

    Xu, Qing; Zhou, Yong-Bo; Zhao, Chang-Qiu; Yin, Shuang-Feng; Han, Li-Biao

    2013-05-01

    Organophosphorus compounds are of high importance in organic synthesis, catalysis, biochemistry, pharmaceuticals, and material science. In this mini review, we summarize our recent studies on transition metal-catalyzed green and atom efficient transformations of P(O)-H bonds to various versatile organophosphorus compounds, including the highly regio- and stereoselective P(O)-H additions to carbon-carbon unsaturated compounds, asymmetric hydrophosphorylation reactions, and dehydrogenative coupling reactions of P(O)-H compounds with carbon-H and heteroatom-H compounds. These new reactions provide efficient, general and practical ways for the preparation of a variety of well-defined functional organophosphorus compounds. Mechanistic aspects related to the catalytic processes are also discussed.

  15. First total synthesis of a natural product containing a chiral, beta-diketone: synthesis and stereochemical reassignment of siphonarienedione and siphonarienolone.

    PubMed

    Calter, Michael A; Liao, Wensheng

    2002-11-06

    The first total syntheses of siphonarienolone and siphonarienedione are described. The development of a stereoselective synthesis of beta-diketones facilitated the synthesis of the latter compound. The synthesis of the structures proposed for the natural products afforded compounds whose spectral data did not match those of the natural products. However, the synthesis of compounds isomeric to the proposed structures at C(4) and C(5) afforded compounds identical to the natural products, thereby reassigning the stereochemistry of the natural products.

  16. Sequential Infiltration Synthesis of Doped Polymer Films with Tunable Electrical Properties for Efficient Triboelectric Nanogenerator Development.

    PubMed

    Yu, Yanhao; Li, Zhaodong; Wang, Yunming; Gong, Shaoqin; Wang, Xudong

    2015-09-02

    Doping polymer with AlOx via sequential infiltration synthesis enables bulk modification of triboelectric polymers with tunable electric or dielectric properties, which broadens the material selection and achieves a durable performance gain of triboelectric nanogenerators.

  17. Iridium-Catalyzed Dynamic Kinetic Isomerization: Expedient Synthesis of Carbohydrates from Achmatowicz Rearrangement Products.

    PubMed

    Wang, Hao-Yuan; Yang, Ka; Bennett, Scott R; Guo, Sheng-rong; Tang, Weiping

    2015-07-20

    A highly stereoselective dynamic kinetic isomerization of Achmatowicz rearrangement products was discovered. This new internal redox isomerization provided ready access to key intermediates for the enantio- and diastereoselective synthesis of a series of naturally occurring sugars. The nature of the de novo synthesis also enables the preparation of both enantiomers.

  18. Chemoselective efficient synthesis of functionalized β-oxonitriles through cyanomethylation of Weinreb amides.

    PubMed

    Mamuye, Ashenafi Damtew; Castoldi, Laura; Azzena, Ugo; Holzer, Wolfgang; Pace, Vittorio

    2015-02-21

    A synthesis of β-oxonitriles is reported via the generation of R(1)R(2)CLiCN species followed by the trapping with variously decorated Weinreb amides. The optimization study revealed that lithiation of acetonitriles is best accomplished by deprotonation with MeLi-LiBr at low temperature. The protocol can be conveniently adapted to the synthesis of α-mono or α,α-disubstituted cyanoketones. (15)N- and (17)O-NMR data are reported for selected compounds.

  19. I. Development of Metal-Mediated SPOT-Synthesis Methods for the Efficient Construction of Small-Molecule Macroarrays. II. Design and Synthesis of Novel Bacterial Biofilm Inhibitors

    NASA Astrophysics Data System (ADS)

    Frei, Reto

    I. The use of small molecule probes to explore biological phenomena has become a valuable tool in chemical biology. As a result, methods that permit the rapid synthesis and biological evaluation of such compounds are highly sought-after. The small molecule macroarray represents one such approach for the synthesis and identification of novel bioactive agents. Macroarrays are readily constructed via the SPOT-synthesis technique on planar cellulose membranes, yielding spatially addressed libraries of ˜10-1000 unique compounds. We sought to expand the arsenal of chemical reactions compatible with this solid-phase platform, and developed highly efficient SPOT-synthesis protocols for the Mizoroki-Heck, Suzuki-Miyaura, and copper-catalyzed azide-alkyne cycloaddition reaction. We demonstrated that these metal-mediated reactions can be implemented, either individually or sequentially, for the efficient construction of small molecules in high purity on rapid time scales. Utilizing these powerful C-C and C-N bond forming coupling reactions, we constructed a series of macroarrays based on novel stilbene, phenyl-naphthalene, and triazole scaliblds. Subsequent biological testing of the stilbene and phenyl-naphthalene libraries revealed several potent antagonists and agonists, respectively, of the quorum sensing (QS) receptor LuxR in Vibrio fischeri. II. Bacteria living within biofilms are notorious for their resistance to known antibiotic agents, and constitute a major human health threat. Methods to attenuate biofilm growth would have a significant impact on the management of bacterial infections. Despite intense research efforts, small molecules capable of either inhibiting or dispersing biolilms remain scarce. We utilized natural products with purported anti-biofilm or QS inhibitory activity as sources of structural insight to guide the synthesis of novel biofilm modulators with improved activities. These studies revealed 2-aminobenzimidazole derivatives as highly potent

  20. Microwave assisted efficient synthesis of diphenyl substituted pyrazoles using PEG-600 as solvent - A green approach.

    PubMed

    Ganapathi, M; Jayaseelan, D; Guhanathan, S

    2015-11-01

    A conventional and microwave assisted efficient synthesis of diphenyl substituted pyrazole using PEG 600 as green solvent has been described. A relatively shorter reaction time with excellent yield of the piperidine mediated protocol has been attracted economically attractive and eco-friendly. All newly synthesized compounds were characterized by standard spectroscopic techniques viz., UV-visible, FT-IR, (1)H-NMR and Mass spectra. The anti-microbial activities of compounds have also been tested using Minimum Inhibitory Concentration (MIC) method with two different microorganisms Staphylococcus aureus (MTCC3381) and Escherichia coli (MTCC739). The results of the antimicrobial activity revealed that the diphenyl substituted pyrazole derivatives have nice inhibiting nature against both types of bacteria of present investigation than corresponding chalcones. Since, the work has been focused on green chemical approach towards the synthesis, this protocol may be recommended for eco-friendly applications.

  1. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.

    PubMed

    Melton, D A; Krieg, P A; Rebagliati, M R; Maniatis, T; Zinn, K; Green, M R

    1984-09-25

    A simple and efficient method for synthesizing pure single stranded RNAs of virtually any structure is described. This in vitro transcription system is based on the unusually specific RNA synthesis by bacteriophage SP6 RNA polymerase which initiates transcription exclusively at an SP6 promoter. We have constructed convenient cloning vectors that contain an SP6 promoter immediately upstream from a polylinker sequence. Using these SP6 vectors, optimal conditions have been established for in vitro RNA synthesis. The advantages and uses of SP6 derived RNAs as probes for nucleic acid blot and solution hybridizations are demonstrated. We show that single stranded RNA probes of a high specific activity are easy to prepare and can significantly increase the sensitivity of nucleic acid hybridization methods. Furthermore, the SP6 transcription system can be used to prepare RNA substrates for studies on RNA processing (1,5,9) and translation (see accompanying paper).

  2. Synthesis of a Sulfonated Two-Dimensional Covalent Organic Framework as an Efficient Solid Acid Catalyst for Biobased Chemical Conversion.

    PubMed

    Peng, Yongwu; Hu, Zhigang; Gao, Yongjun; Yuan, Daqiang; Kang, Zixi; Qian, Yuhong; Yan, Ning; Zhao, Dan

    2015-10-12

    Because of limited framework stability tolerance, de novo synthesis of sulfonated covalent organic frameworks (COFs) remains challenging and unexplored. Herein, a sulfonated two-dimensional crystalline COF, termed TFP-DABA, was synthesized directly from 1,3,5-triformylphloroglucinol and 2,5-diaminobenzenesulfonic acid through a previously reported Schiff base condensation reaction, followed by irreversible enol-to-keto tautomerization, which strengthened its structural stability. TFP-DABA is a highly efficient solid acid catalyst for fructose conversion with remarkable yields (97 % for 5-hydroxymethylfurfural and 65 % for 2,5-diformylfuran), good chemoselectivity, and good recyclability. The present study sheds light on the de novo synthesis of sulfonated COFs as novel solid acid catalysts for biobased chemical conversion.

  3. A green and efficient protocol for the synthesis of quinoxaline, benzoxazole and benzimidazole derivatives using heteropolyanion-based ionic liquids: as a recyclable solid catalyst.

    PubMed

    Vahdat, Seyed Mohammad; Baghery, Saeed

    2013-09-01

    In this paper, we introduce two nonconventional ionic liquid compounds which are composed of propane sulfonate functionalized organic cations and heteropolyanions as green solid acid catalysts for the highly efficient and green synthesis of 2,3-disubstitutedquinoxaline derivatives. These ionic liquids are in the solid state at room temperature and the synthesis is carried out via the one-pot condensation reaction of various o-phenylenediamine with 1,2-diketone derivatives. Benzoxazole and benzimidazole derivatives were also synthesized by these novel catalysts via the one-pot condensation from reaction orthoester with o-aminophenol (synthesis of benzoxazole derivatives) and ophenylenediamine (synthesis of benzimidazole derivatives). All experiments successfully resulted in the desired products. The described novel synthesis method has several advantages of safety, mild condition, high yields, short reaction times, simplicity and easy workup compared to the traditional method of synthesis.

  4. Stereoselective Reduction of Prochiral Ketones by Plant and Microbial Biocatalysts

    PubMed Central

    Javidnia, K.; Faghih-Mirzaei, E.; Miri, R.; Attarroshan, M.; Zomorodian, K.

    2016-01-01

    Chiral alcohols are the key chiral building blocks to many enantiomerically pure pharmaceuticals. The biocatalytic approach in asymmetric reduction of corresponding prochiral ketones to the preparation of these optically pure substances is one of the most promising routes. The stereoselective reduction of different kinds of prochiral ketones catalyzed by various plants and microorganisms was studied in this work. Benzyl acetoacetate, methyl 3-oxopentanoate, ethyl 3-oxopentanoate, and ethyl butyryl acetate were chosen as the model substrates for β-ketoesters. Benzoyl acetonitrile, 3-chloro propiophenone, and 1-acetyl naphthalene were chosen as aromatic aliphatic ketones. Finally, 2-methyl benzophenone and 4-chloro benzophenone were selected as diaryl ketones. Plant catalysis was conducted by Daucus carota, Brassica rapa, Brassica oleracea, Pastinaca sativa, and Raphnus sativus. For microbial catalysis, Aspergillus foetidus, Penicillum citrinum, Saccharomyces carlbergensis, Pichia fermentans, and Rhodotrula glutinis were chosen. Chiral alcohols were obtained in high yields and with optical purity. A superiority in the microorganisms' performance in the bioreduction of prochiral ketones was detected. Among microorganisms, Rhodotrula glutinis showed remarkable results with nearly all substrates and is proposed for future studies. PMID:27168684

  5. Stereoselective degradation of Diclofop-methyl during alcohol fermentation process.

    PubMed

    Lu, Yuele; Diao, Jinling; Gu, Xu; Zhang, Yanfeng; Xu, Peng; Wang, Peng; Zhou, Zhiqiang

    2011-05-01

    Stereoselective degradation of Diclofop-methyl (DM) has been found in alcohol fermentation of grape must and sucrose solution with dry yeast. A method was developed for separation and determination the two enantiomers of DM during the fermentation process by high-performance liquid chromatography based on cellulose tri-(3,5-dimethylphenyl-carbamate) chiral stationary phase. The results showed that the enantiomers of DM degraded following the first-order kinetics in the sucrose solution and the degradation of DM enantiomers in grape must were biphasic (slow-fast-slow process). In the sucrose solution, half lives of (+)-(R)-DM and (-)-(S)-DM were calculated to be 8.5 h and 3.1 h, respectively. In the grape must, half life of (+)-(R)-DM was calculated to be 41.7 h while (-)-(S)-DM was 16.0 h. The result was that (-)-(S)-enantiomer degraded faster than the (+)-(R)-enantiomer in both alcohol fermentation. The results also showed that the differences of the enantioselective degradation of DM depended on the fermentation matrix. DM was configurationally stable in fermentation, showing no interconversion of (-)-(S)- to (+)-(R)- enantiomer, and vice-versa.

  6. Studies on A Urea Directed Stork-Crabtree Hydrogenation. Synthesis of C1–C9 Subunit of (+)-Zincophorin

    PubMed Central

    Song, Zhenlei; Hsung, Richard P.; Lu, Ting; Lohse, Andrew G.

    2008-01-01

    A detailed account on the stereoselective synthesis of the C1–C9 subunit of (+)-zincophorin is described here. This approach features the first application of a stereoselective inverse electron demand hetero [4 + 2] cycloaddition of chiral allenamides in natural product synthesis. The C1–C9 subunit matches Cossy’s intermediate, thereby constituting a formal total synthesis. In addition, details of an unusual urea directed Stork-Crabtree hydrogenation observed during these efforts is also disclosed here. PMID:17979293

  7. Short and Efficient Synthesis of Alkyl- and Aryl-Ortho-Hydroxy-Anilides and their Antibiotic Activity

    PubMed Central

    Krauß, Jürgen; Plesch, Eva; Clausen, Sabine; Bracher, Franz

    2014-01-01

    Abstract Ortho-hydroxy-anilides are part of natural products like the new antibiotics platencin (A) and platensimycin (B). An important step in the total synthesis of these antibiotics or their derivatives is the preparation of the o-hydroxy-anilide partial structure. The presented method allows the preparation of o-hydroxy-anilides and o-dihydroxy-anilides from 2-nitrophenol esters in a one-step synthesis without protecting the hydroxy group. Aryl- and alkyl-anilides were prepared following this method as simple analogues of platensimycin (A). The resulting compounds were tested in an agar diffusion assay for their antibiotic potency. PMID:25853064

  8. Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis.

    PubMed

    Hack, Daniel; Dürr, Alexander B; Deckers, Kristina; Chauhan, Pankaj; Seling, Nico; Rübenach, Lukas; Mertens, Lucas; Raabe, Gerhard; Schoenebeck, Franziska; Enders, Dieter

    2016-01-26

    A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments.

  9. A Synthesis of the Carbocyclic Core of Maoecrystal V

    PubMed Central

    Lazarski, Kiel E.; Hu, Dennis X.; Stern, Charlotte L.; Thomson, Regan J.

    2010-01-01

    An approach towards the synthesis of the complex polycyclic diterpene maoecrystal V (1) is described. Construction of the advanced tetracyclic core structure (i.e., 19) was achieved in 13 steps from 3,3-dimethylcyclohexanone (6) by employing a stereoselective Nazarov cyclization followed by a Diels–Alder reaction to forge the two contiguous quaternary stereocenters. PMID:20521835

  10. Total Synthesis of the Galbulimima Alkaloid (−)-GB17**

    PubMed Central

    Larson, Reed T.; Clift, Michael D.

    2012-01-01

    A Tale of Two Michaels The first enantioselective total synthesis of (−)-GB17 is reported. Construction of this unique naphthoquinolizinone skeleton was achieved by two stereoselective intramolecular Michael additions. The first of these Michael additions is controlled by the use of a chiral organocatalyst, while the second cyclization is under substrate control and proceeds with concomitant lactam formation. PMID:22287499

  11. Short asymmetric synthesis of (-)- and (+)-cis-lauthisan.

    PubMed

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

    2005-05-12

    The asymmetric synthesis of both enantiomers of cis-lauthisan (3) is achieved in only six steps from diethyl pimelate (4), the key steps being the diastereodivergent reduction of beta-ketosulfoxide 7 and the highly cis-stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization of enantiopure hydroxy sulfinyl ketones (S)-14 and (R)-14.

  12. Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis

    PubMed Central

    Hack, Daniel; Dürr, Alexander B; Deckers, Kristina; Chauhan, Pankaj; Seling, Nico; Rübenach, Lukas; Mertens, Lucas; Raabe, Gerhard; Schoenebeck, Franziska; Enders, Dieter

    2016-01-01

    A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments. PMID:26676875

  13. Efficient room temperature aqueous Sb2S3 synthesis for inorganic-organic sensitized solar cells with 5.1% efficiencies.

    PubMed

    Gödel, Karl C; Choi, Yong Chan; Roose, Bart; Sadhanala, Aditya; Snaith, Henry J; Seok, Sang Il; Steiner, Ullrich; Pathak, Sandeep K

    2015-05-21

    Sb2S3 sensitized solar cells are a promising alternative to devices employing organic dyes. The manufacture of Sb2S3 absorber layers is however slow and cumbersome. Here, we report the modified aqueous chemical bath synthesis of Sb2S3 absorber layers for sensitized solar cells. Our method is based on the hydrolysis of SbCl3 to complex antimony ions decelerating the reaction at ambient conditions, in contrast to the usual low temperature deposition protocol. This simplified deposition route allows the manufacture of sensitized mesoporous-TiO2 solar cells with power conversion efficiencies up to η = 5.1%. Photothermal deflection spectroscopy shows that the sub-bandgap trap-state density is lower in Sb2S3 films deposited with this method, compared to standard deposition protocols.

  14. Tailor Made Synthesis of T-Shaped and π-STACKED Dimers in the Gas Phase: Concept for Efficient Drug Design and Material Synthesis

    NASA Astrophysics Data System (ADS)

    Kumar, Sumit; Das, Aloke

    2013-06-01

    Non-covalent interactions play a key role in governing the specific functional structures of biomolecules as well as materials. Thus molecular level understanding of these intermolecular interactions can help in efficient drug design and material synthesis. It has been found from X-ray crystallography that pure hydrocarbon solids (i.e. benzene, hexaflurobenzene) have mostly slanted T-shaped (herringbone) packing arrangement whereas mixed solid hydrocarbon crystals (i.e. solid formed from mixtures of benzene and hexafluorobenzene) exhibit preferentially parallel displaced (PD) π-stacked arrangement. Gas phase spectroscopy of the dimeric complexes of the building blocks of solid pure benzene and mixed benzene-hexafluorobenzene adducts exhibit similar structural motifs observed in the corresponding crystal strcutures. In this talk, I will discuss about the jet-cooled dimeric complexes of indole with hexafluorobenzene and p-xylene in the gas phase using Resonant two photon ionzation and IR-UV double resonance spectroscopy combined with quantum chemistry calculations. In stead of studying benzene...p-xylene and benzene...hexafluorobenzene dimers, we have studied corresponding indole complexes because N-H group is much more sensitive IR probe compared to C-H group. We have observed that indole...hexafluorobenzene dimer has parallel displaced (PD) π-stacked structure whereas indole...p-xylene has slanted T-shaped structure. We have shown here selective switching of dimeric structure from T-shaped to π-stacked by changing the substituent from electron donating (-CH3) to electron withdrawing group (fluorine) in one of the complexing partners. Thus, our results demonstrate that efficient engineering of the non-covalent interactions can lead to efficient drug design and material synthesis.

  15. Characterization of a Zinc-Containing Alcohol Dehydrogenase with Stereoselectivity from the Hyperthermophilic Archaeon Thermococcus guaymasensis▿

    PubMed Central

    Ying, Xiangxian; Ma, Kesen

    2011-01-01

    An alcohol dehydrogenase (ADH) from hyperthermophilic archaeon Thermococcus guaymasensis was purified to homogeneity and was found to be a homotetramer with a subunit size of 40 ± 1 kDa. The gene encoding the enzyme was cloned and sequenced; this gene had 1,095 bp, corresponding to 365 amino acids, and showed high sequence homology to zinc-containing ADHs and l-threonine dehydrogenases with binding motifs of catalytic zinc and NADP+. Metal analyses revealed that this NADP+-dependent enzyme contained 0.9 ± 0.03 g-atoms of zinc per subunit. It was a primary-secondary ADH and exhibited a substrate preference for secondary alcohols and corresponding ketones. Particularly, the enzyme with unusual stereoselectivity catalyzed an anti-Prelog reduction of racemic (R/S)-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol. The optimal pH values for the oxidation and formation of alcohols were 10.5 and 7.5, respectively. Besides being hyperthermostable, the enzyme activity increased as the temperature was elevated up to 95°C. The enzyme was active in the presence of methanol up to 40% (vol/vol) in the assay mixture. The reduction of ketones underwent high efficiency by coupling with excess isopropanol to regenerate NADPH. The kinetic parameters of the enzyme showed that the apparent Km values and catalytic efficiency for NADPH were 40 times lower and 5 times higher than those for NADP+, respectively. The physiological roles of the enzyme were proposed to be in the formation of alcohols such as ethanol or acetoin concomitant to the NADPH oxidation. PMID:21515780

  16. Total synthesis of atropurpuran

    PubMed Central

    Gong, Jing; Chen, Huan; Liu, Xiao-Yu; Wang, Zhi-Xiu; Nie, Wei; Qin, Yong

    2016-01-01

    Due to their architectural intricacy and biological significance, the synthesis of polycyclic diterpenes and their biogenetically related alkaloids have been the subject of considerable interest over the last few decades, with progress including the impressive synthesis of several elusive targets. Despite tremendous efforts, conquering the unique structural types of this large natural product family remains a long-term challenge. The arcutane diterpenes and related alkaloids, bearing a congested tetracyclo[5.3.3.04,9.04,12]tridecane unit, are included in these unsolved enigmas. Here we report a concise approach to the construction of the core structure of these molecules and the first total synthesis of (±)-atropurpuran. Pivotal features of the synthesis include an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, sequential aldol and ketyl-olefin cyclizations to assemble the highly caged framework, and a chemoselective and stereoselective reduction to install the requisite allylic hydroxyl group in the target molecule. PMID:27387707

  17. Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

    PubMed Central

    An, Qi; Hassan, Youssef; Yan, Xiaotong; Krolla-Sidenstein, Peter; Mohammed, Tawheed; Lang, Mathias; Bräse, Stefan

    2017-01-01

    Conjugated microporous polymers (CMPs) are materials of low density and high intrinsic porosity. This is due to the use of rigid building blocks consisting only of lightweight elements. These materials are usually stable up to temperatures of 400 °C and are chemically inert, since the networks are highly crosslinked via strong covalent bonds, making them ideal candidates for demanding applications in hostile environments. However, the high stability and chemical inertness pose problems in the processing of the CMP materials and their integration in functional devices. Especially the application of these materials for membrane separation has been limited due to their insoluble nature when synthesized as bulk material. To make full use of the beneficial properties of CMPs for membrane applications, their synthesis and functionalization on surfaces become increasingly important. In this respect, we recently introduced the solid liquid interfacial layer-by-layer (LbL) synthesis of CMP-nanomembranes via Cu catalyzed azide–alkyne cycloaddition (CuAAC). However, this process featured very long reaction times and limited scalability. Herein we present the synthesis of surface grown CMP thin films and nanomembranes via light induced thiol–yne click reaction. Using this reaction, we could greatly enhance the CMP nanomembrane synthesis and further broaden the variability of the LbL approach.

  18. The Origins of Stereoselectivity in the α-Alkylation of Chiral Hydrazones

    PubMed Central

    Krenske, Elizabeth H.; Lim, Daniel; Wengryniuk, Sarah E.

    2010-01-01

    Density functional theory calculations and experiment reveal the origin of stereoselectivity in the deprotonation–alkylation of chiral N-amino cyclic carbamate (ACC) hydrazones. When the ACC is a rigid, camphor-derived carbamate, the two conformations of the azaenolate intermediate differ in energy due to conformational effects within the oxazolidinone ring and steric interactions between the ACC and the azaenolate. An electrophile adds selectively to the less-hindered π-face of the azaenolate. Although it was earlier reported that use of ACC auxiliaries led to α-alkylated ketones with ers of 82:18 to 98:2, B3LYP calculations predict higher stereoselectivity. Direct measurement of the dr of an alkylated hydrazone prior to removal of the auxiliary confirms this prediction; the removal of the auxiliary can compromise the overall stereoselectivity of the process. PMID:21070023

  19. Stereoselective C-glycosidation of D-fucose derivatives directed by the protective groups.

    PubMed

    Cortezano-Arellano, Omar; Meléndez-Becerra, Camilo A; Cortés, Fernando; Sartillo-Piscil, Fernando; Cordero-Vargas, Alejandro

    2014-07-01

    Stereoselectivity in the C-glycosidation of lactones derived from D-fucose by following Kishi's method, which involves the addition of a nucleophile onto a carbohydrate-derived lactone and subsequent reduction of the lactol, was found to be reliant on the nature of the C2 and C3 protective groups. Lactones bearing TBDMS protecting groups selectively afford 1,3-trans products (α anomer), in which the stereoselective outcome is in apparent concordance with Woerpel's model. On the other hand, their benzylated congeners produce the 1,3-cis products (β anomer) as the major diastereoisomers. The latter results suggest an abnormal behavior during the stereoselective nucleophilic substitution at the anomeric position of the benzylated lactones.

  20. Selective synthesis of vitamin K3 over mesoporous NbSBA-15 catalysts synthesized by an efficient hydrothermal method.

    PubMed

    Selvaraj, M; Park, D-W; Kim, I; Kawi, S; Ha, C S

    2012-08-28

    Well hexagonally ordered NbSBA-15 catalysts synthesized by an efficient hydrothermal method were used, for the first time, for the selective synthesis of vitamin K(3) by liquid-phase oxidation of 2-methyl-1-naphthol (2MN1-OH) under various reaction conditions. The recyclable NbSBA-15 catalysts were also reused to find their catalytic activities. To investigate the leaching of non-framework niobium species on the surface of silica networks, the results of original and recyclable NbSBA-15 catalysts were correlated and compared. To find an optimum condition for the selective synthesis of vitamin K(3), the washed NbSBA-15(2.2pH) was extensively used in this reaction with various reaction parameters such as temperature, time and ratios of reactant (2M1N-OH to H(2)O(2)), and the obtained results were also demonstrated. Additionally, the liquid-phase oxidation of 2M1N-OH was carried out with different solvents to find the best solvent with a good catalytic activity. Based on the all catalytic studies, the vitamin K(3) selectivity (97.3%) is higher in NbSBA-15(2.2pH) than that of other NbSBA-15 catalysts, and the NbSBA-15(2.2pH) is found to be a highly active and eco-friendly heterogeneous catalyst for the selective synthesis of vitamin K(3).

  1. Highly efficient synthesis of endomorphin-2 under thermodynamic control catalyzed by organic solvent stable proteases with in situ product removal.

    PubMed

    Xu, Jiaxing; Sun, Honglin; He, Xuejun; Bai, Zhongzhong; He, Bingfang

    2013-02-01

    An efficient enzymatic synthesis of endomorphin-2 (EM-2) was achieved using organic solvent stable proteases in nonaqeous media, based on thermodynamic control and an in situ product removal methodology. The high stability of biocatalysts in organic solvents enabled the aleatoric modulation of the nonaqueous reaction media to shift thermodynamic equilibrium toward synthesis. Peptide Boc-Phe-Phe-NH2 was synthesized with a high yield of 96% by the solvent stable protease WQ9-2 in monophase medium with an economical molar ratio of the substrate of 1:1. The tetrapeptide Boc-Tyr-Pro-Phe-Phe-NH2 was synthesized with a yield of 88% by another organic solvent tolerant protease PT121 from Boc-Tyr-Pro-OH and Phe-Phe-NH2 in an organic-aqueous biphasic system. The reaction-separation coupling in both enzymatic processes provides "driving forces" for the synthetic reactions and gives a high yield and high productivity without purification of the intermediate, thereby making the synthesis more amenable to scale-up.

  2. Efficient Cu(OTf)2-catalyzed synthesis of novel and diverse 2,3-dihydroquinazolin-4(1H)-ones.

    PubMed

    Zhu, Xiaoyan; Kang, So Rang; Xia, Likai; Lee, Jihye; Basavegowda, Nagaraj; Lee, Yong Rok

    2015-02-01

    An efficient one-pot synthesis of various 2,3-dihydroquinazolin-4(1H)-one derivatives was accomplished using Cu(OTf)2-catalyzed multi-component reactions between isatoic anhydride, ketones, and amines. The method has several significant advantages; mild reaction conditions, easy handling, and efficiency of catalyst.

  3. Convergent and stereospecific synthesis of complex skipped polyenes and polyunsaturated fatty acids.

    PubMed

    Macklin, Todd K; Micalizio, Glenn C

    2010-08-01

    Skipped polyenes (that is, 1,4-dienes and higher homologues) are stereodefined components of a vast array of biologically important natural products, including polyunsaturated fatty acids. Although widespread in nature, these architectures are generally considered to represent significant barriers to efficient chemical synthesis. Partial reduction of skipped poly-ynes provides a pathway to a subset of such structures, but general chemical methods for the preparation of skipped polyenes that contain varied stereochemistries and substitution patterns are lacking. Here, we describe a metal-promoted reductive cross-coupling reaction between vinylcyclopropanes and alkynes (or vinylsilanes) that provides stereoselective access to a diverse array of skipped polyenes through a process that establishes one C-C bond, generates up to three stereodefined alkenes, and can be used to introduce stereogenic centres at the central positions of the skipped polyene motif. We also demonstrate the significance of the present bond construction by preparing substituted and stereodefined polyunsaturated synthetic fatty acids.

  4. Energy- and carbon-efficient synthesis of functionalized small molecules in bacteria using non-decarboxylative Claisen condensation reactions.

    PubMed

    Cheong, Seokjung; Clomburg, James M; Gonzalez, Ramon

    2016-05-01

    Anabolic metabolism can produce an array of small molecules, but yields and productivities are low owing to carbon and energy inefficiencies and slow kinetics. Catabolic and fermentative pathways, on the other hand, are carbon and energy efficient but support only a limited product range. We used carbon- and energy-efficient non-decarboxylative Claisen condensation reactions and subsequent β-reduction reactions, which can accept a variety of functionalized primers and functionalized extender units and operate in an iterative manner, to synthesize functionalized small molecules. Using different ω- and ω-1-functionalized primers and α-functionalized extender units in combination with various termination pathways, we demonstrate the synthesis of 18 products from 10 classes, including ω-phenylalkanoic, α,ω-dicarboxylic, ω-hydroxy, ω-1-oxo, ω-1-methyl, 2-methyl, 2-methyl-2-enolic and 2,3-dihydroxy acids, β-hydroxy-ω-lactones, and ω-1-methyl alcohols.

  5. Continuous-Flow Microwave Synthesis of Metal-Organic Frameworks: A Highly Efficient Method for Large-Scale Production.

    PubMed

    Taddei, Marco; Steitz, Daniel Antti; van Bokhoven, Jeroen Anton; Ranocchiari, Marco

    2016-03-01

    Metal-organic frameworks are having a tremendous impact on novel strategic applications, with prospective employment in industrially relevant processes. The development of such processes is strictly dependent on the ability to generate materials with high yield efficiency and production rate. We report a versatile and highly efficient method for synthesis of metal-organic frameworks in large quantities using continuous flow processing under microwave irradiation. Benchmark materials such as UiO-66, MIL-53(Al), and HKUST-1 were obtained with remarkable mass, space-time yields, and often using stoichiometric amounts of reactants. In the case of UiO-66 and MIL-53(Al), we attained unprecedented space-time yields far greater than those reported previously. All of the syntheses were successfully extended to multi-gram high quality products in a matter of minutes, proving the effectiveness of continuous flow microwave technology for the large scale production of metal-organic frameworks.

  6. Evolving P450pyr Monooxygenase for Regio- and Stereoselective Hydroxylations.

    PubMed

    Yang, Yi; Li, Zhi

    2015-01-01

    P450pyr monooxygenase from Sphingomonas sp. HXN-200 catalysed the regio- and stereoselective hydroxylation at a non-activated carbon atom, a useful but challenging reaction in classic chemistry, with unique substrate specificity for a number of alicyclic compounds. New P450pyr mutants were developed by directed evolution with improved catalytic performance, thus significantly extending the application of the P450pyr monooxygenase family in biohydroxylation to prepare useful and valuable chiral alcohols. Directed evolution of P450pyr created new enzymes with improved S-enantioselectivity or R-enantioselectivity for the hydroxylation of N-benzyl pyrrolidine, enhanced regioselectivity for the hydroxylation of N-benzyl pyrrolidinone, and increased enantioselectivity for the hydroxylation of N-benzyl piperidinone, respectively. Directed evolution of P450pyr generated also mutants with fully altered regioselectivity (from terminal to subterminal) and newly created excellent S-enantioselectivity for the biohydroxylation of n-octane and propylbenzene, respectively, providing new opportunities for the regio- and enantioselective alkane functionalization. New P450pyr mutants were engineered as the first catalyst for highly selective terminal hydroxylation of n-butanol to 1,4-butanediol. Several novel, accurate, sensitive, simple, and HTS assays based on colorimetric or MS detection for measuring the enantio- and/or regioselectivity of hydroxylation were developed and proven to be practical in directed evolution. The P450pyr X-ray structure was obtained and used to guide the evolution. In silico modelling and substrate docking provided some insight into the influence of several important amino acid mutations of the engineered P450pyr mutants on the altered or enhanced regio- and enantioselectivity as well as new substrate acceptance. The obtained information and knowledge is useful for further engineering of P450pyr for other hydroxylations and oxidations.

  7. Development of specificity and stereoselectivity of rat brain dopamine receptors.

    PubMed

    Miller, J C; Friedhoff, A J

    1986-01-01

    Prenatal exposure to the neuroleptic haloperidol has been reported to produce an enduring decrement in the number of dopamine D2 receptors in rat striatum and a persistent diminution of a dopamine dependent behavior, stereotypy. The ontogeny of rat brain dopamine binding sites has been studied in terms of the kinetic properties and phenotypic specificity in rat fetal brain through early postnatal development. Sites showing some properties of the D2 binding site can be found prior to gestational day (GD) 18, can be labeled with [3H]dopamine or [3H]spiroperidol and can be displaced with dopaminergic agonists and antagonists. Saturation kinetics for specific [3H]spiroperidol has previously been found to occur on or about GD 18. It is of interest that the critical period for the prenatal effect of haloperidol to reduce striatal D2 binding sites, GD's 15-18, coincides with the period during which dopamine binding sites lack true specificity, but can be labeled with dopaminergic ligands. In these experiments the development of stereoselectivity of brain dopamine binding sites has been examined. When rat mothers were given either the neuroleptic (+)-butaclamol or its therapeutically inactive isomer (-)-butaclamol during the critical period GD's 15-18, the number of [3H]spiroperidol binding sites in striata of offspring was significantly reduced by both stereoisomers. This is in marked contrast to the postnatal treatment effect by a neuroleptic in which upregulation of striatal D2 binding sites occurs only by treatment with the therapeutically active isomer (+)-butaclamol. In vitro studies of the direct effect of the stereoisomers of butaclamol indicate that the recognition sites detected during fetal brain development with [3H]spiroperidol do not distinguish between the isomers of butaclamol.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. A modern approach to the synthesis of 2-(4-chlorophenyl)[2-(14)C]thiazol-4-ylacetic acid ([(14)C] fenclozic acid) and its acyl glucuronide metabolite.

    PubMed

    Killick, David A; Bushby, Nick

    2013-01-01

    An updated approach to the 1960s synthesis of [(14)C] fenclozic acid from labelled potassium cyanide is presented. By employing modern synthetic methodology and purification techniques, many of the inherent hazards in the original synthesis are avoided or significantly reduced. The concomitant labelled stereoselective synthesis of the key acyl glucuronide metabolite (the 1-β-O-acyl glucuronide) is also described.

  9. Asymmetric Synthesis of Ramariolides A and C through Bimetallic Cascade Cyclization and Z-E Isomerization Reaction.

    PubMed

    Pal, Pratik; Nanda, Samik

    2017-03-03

    A short and flexible asymmetric synthesis of ramariolides A and C was accomplished. A bimetallic catalytic system consisting of Pd-Cu-mediated cascade cyclization, unprecedented Z-E isomerization by a Ru-based metathesis catalyst, and late-stage stereoselective epoxidation are the key steps involved in the synthesis.

  10. Reaction design, discovery, and development as a foundation to function-oriented synthesis.

    PubMed

    Micalizio, Glenn C; Hale, Sarah B

    2015-03-17

    Convergent C-C bond-forming reactions define the fabric of organic synthesis and, when applied in complex molecule synthesis, can have a profound impact on efficiency by decreasing the longest linear sequence of transformations required to convert simple starting materials to complex targets. Despite their well-appreciated strategic significance, campaigns in natural product synthesis typically embrace only a small suite of reactivity to achieve such bond construction (i.e., nucleophilic addition to polarized π-bonds, nucleophilic substitution, cycloaddition, and metal-catalyzed "cross-coupling"), therefore limiting the sites at which convergent coupling chemistry can be strategically employed. In our opinion, it is far too often that triumphs in the field are defined by chemical sequences that do not address the challenges associated with discovery, development, and production of natural product-inspired agents. We speculated that advancing an area of chemical reactivity not represented in the few well-established strategies for convergent C-C bond formation may lead to powerful new retrosynthetic relationships that could simplify approaches to the syntheses of a variety of different classes of natural products. Our studies ultimately embraced the pursuit of strategies to control the course of metallacycle-mediated "cross-coupling" between substrates containing sites of simple π-unsaturation (ubiquitous functionality in organic chemistry including alkenes, alkynes, allenes, aldehydes, and imines, among others). In just eight years since our initial publication in this area, we have defined over 20 stereoselective intermolecular C-C bond-forming reactions that provide access to structural motifs of relevance for the synthesis of polyketides, fatty acids, alkaloids, and terpenes, while doing so in a direct and stereoselective fashion. These achievements continue to serve as the foundation of my group's activity in natural product and function-oriented synthesis

  11. Glycosynthases enable a highly efficient chemoenzymatic synthesis of N-glycoproteins carrying intact natural N-glycans.

    PubMed

    Huang, Wei; Li, Cishan; Li, Bing; Umekawa, Midori; Yamamoto, Kenji; Zhang, Xinyu; Wang, Lai-Xi

    2009-02-18

    Homogeneous N-glycoproteins carrying defined natural N-glycans are essential for detailed structural and functional studies. The transglycosylation activity of the endo-beta-N-acetylglucosaminidases from Arthrobacter protophormiae (Endo-A) and Mucor hiemalis (Endo-M) holds great potential for glycoprotein synthesis, but the wild-type enzymes are not practical for making glycoproteins carrying native N-glycans because of their predominant activity for product hydrolysis. In this article, we report studies of two endoglycosidase-based glycosynthases, EndoM-N175A and EndoA-N171A, and their usefulness in constructing homogeneous N-glycoproteins carrying natural N-glycans. The oligosaccharide oxazoline corresponding to the biantennary complex-type N-glycan was synthesized and tested with the two glycosynthases. The EndoM-N175A mutant was able to efficiently transfer the complex-type glycan oxazoline to a GlcNAc peptide and GlcNAc-containing ribonuclease to form the corresponding homogeneous glycopeptide/glycoprotein. The EndoA-N171A mutant did not recognize the complex-type N-glycan oxazoline but could efficiently use the high-mannose-type glycan oxazoline for transglycosylation. These mutants possess the transglycosylation activity but lack the hydrolytic activity toward the product. Kinetic studies revealed that the dramatically enhanced synthetic efficiency of the EndoA-N171A mutant was due to the significantly reduced hydrolytic activity toward both the Man(9)GlcNAc oxazoline and the product as well as to its enhanced activity for transglycosylation. Thus, the two mutants described here represent the first endoglycosidase-based glycosynthases enabling a highly efficient synthesis of homogeneous natural N-glycoproteins.

  12. Glycosynthases Enable a Highly Efficient Chemoenzymatic Synthesis of N-Glycoproteins Carrying Intact Natural N-Glycans

    PubMed Central

    Huang, Wei; Li, Cishan; Li, Bing; Umekawa, Midori; Yamamoto, Kenji; Zhang, Xinyu; Wang, Lai-Xi

    2009-01-01

    Homogeneous N-glycoproteins carrying defined natural N-glycans are essential for detailed structural and functional studies. The transglycosylation activity of the endo-β-N-acetylglucosaminidases from Arthrobacter protophormiae (Endo-A) and Mucor hiemalis (Endo-M) holds a great potential for glycoprotein synthesis, but the wild type enzymes are not practical for making glycoproteins carrying native N-glycans because of their predominant activity for product hydrolysis. We report in this article the studies on two endoglycosidase-based glycosynthases, EndoM-N175A and EndoA-N171A, and their usefulness for constructing homogeneous N-glycoproteins carrying natural N-glycans. Oligosaccharide oxazoline corresponding to the bi-antennary complex type N-glycan was synthesized and tested with the two glycosynthases. The EndoM-N175A mutant was able to efficiently transfer the complex type glycan oxazoline to a GlcNAc-peptide and GlcNAc-containing ribonuclease to form the corresponding homogeneous glycopeptide/glycoprotein. The EndoA-N171A did not recognize complex type N-glycan oxazoline but could efficient use the high-mannose type glycan oxazoline for transglycosylation. These mutants possess the transglycosylation activity but lack the hydrolytic activity toward the product. Kinetic studies revealed that the dramatically enhanced synthetic efficiency of the EndoA-N171A mutant was due to the significantly reduced hydrolytic activity toward both the Man9GlcNAc oxazoline and the product, as well as its enhanced activity for transglycosylation. Thus, the two mutants described here represent the first endoglycosidase-based glycosynthases enabling a high efficient synthesis of homogeneous natural N-glycoproteins. PMID:19199609

  13. Peptide-Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide.

    PubMed

    Grünenfelder, Claudio E; Kisunzu, Jessica K; Wennemers, Helma

    2016-07-18

    The tripeptide H-dPro-Pro-Asn-NH2 is presented as a catalyst for asymmetric conjugate addition reactions of aldehydes to maleimide. The peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields. The obtained products were readily derivatized to the corresponding pyrrolidines, lactams, lactones, and peptide-like compounds. (1) H NMR spectroscopic, crystallographic, and computational investigations provided insight into the conformational properties of H-dPro-Pro-Asn-NH2 and revealed the importance of hydrogen bonding between the peptide and maleimide for catalyzing the stereoselective C-C bond formation.

  14. Applied reaction dynamics: Efficient synthesis gas production via single collision partial oxidation of methane to CO on Rh(111)

    NASA Astrophysics Data System (ADS)

    Gibson, K. D.; Viste, M.; Sibener, S. J.

    2006-10-01

    Supersonic molecular beams have been used to determine the yield of CO from the partial oxidation of CH4 on a Rh(111) catalytic substrate, CH4+(1/2)O2→CO +2H2, as a function of beam kinetic energy. These experiments were done under ultrahigh vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that there was only a single collision for the CH4 to react with the surface. The fraction of CH4 converted is strongly dependent on the normal component of the incident beam's translational energy, and approaches unity for energies greater than ˜1.3eV. Comparison with a simplified model of the methane-Rh(111) reactive potential gives insight into the barrier for methane dissociation. These results demonstrate the efficient conversion of methane to synthesis gas, CO +2H2, are of interest in hydrogen generation, and have the optimal stoichiometry for subsequent utilization in synthetic fuel production (Fischer-Tropsch or methanol synthesis). Moreover, under the reaction conditions explored, no CO2 was detected, i.e., the reaction proceeded with the production of very little, if any, unwanted greenhouse gas by-products. These findings demonstrate the efficacy of overcoming the limitations of purely thermal reaction mechanisms by coupling nonthermal mechanistic steps, leading to efficient C-H bond activation with subsequent thermal heterogeneous reactions.

  15. Biocompatible PEGylated MoS2 nanosheets: controllable bottom-up synthesis and highly efficient photothermal regression of tumor.

    PubMed

    Wang, Shige; Li, Kai; Chen, Yu; Chen, Hangrong; Ma, Ming; Feng, Jingwei; Zhao, Qinghua; Shi, Jianlin

    2015-01-01

    Two-dimensional transition metal dichalcogenides, particularly MoS2 nanosheets, have been deemed as a novel category of NIR photothermal transducing agent. Herein, an efficient and versatile one-pot solvothermal synthesis based on "bottom-up" strategy has been, for the first time, proposed for the controlled synthesis of PEGylated MoS2 nanosheets by using a novel "integrated" precursor containing both Mo and S elements. This facile but unique PEG-mediated solvothermal procedure endowed MoS2 nanosheets with controlled size, increased crystallinity and excellent colloidal stability. The photothermal performance of nanosheets was optimized via modulating the particulate size and surface PEGylation. PEGylated MoS2 nanosheets with desired photothermal conversion performance and excellent colloidal and photothermal stability were further utilized for highly efficient photothermal therapy of cancer in a tumor-bearing mouse xenograft. Without showing observable in vitro and in vivo hemolysis, coagulation and toxicity, the optimized MoS2-PEG nanosheets showed promising in vitro and in vivo anti-cancer efficacy.

  16. Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and affects plant development in rice.

    PubMed

    Shi, Yanyun; Liu, Xiangling; Li, Rui; Gao, Yaping; Xu, Zuopeng; Zhang, Baocai; Zhou, Yihua

    2014-07-01

    The ribosome is the basic machinery for translation, and biogenesis of ribosomes involves many coordinated events. However, knowledge about ribosomal dynamics in higher plants is very limited. This study chose a highly conserved trans-factor, the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O. sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a truncated nuclear localization sequence (OsNMD3(ΔNLS)) was retained in the cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S particles and disturbing the assembly of ribosome subunits. Analyses of the transactivation activity and cellulose biosynthesis level revealed low protein synthesis efficiency in the transgenic plants compared with the wild-type plants. Pharmaceutical treatments demonstrated structural alterations in ribosomes in the transgenic plants. Moreover, global expression profiles of the wild-type and transgenic plants were investigated using the Illumina RNA sequencing approach. These expression profiles suggested that overexpression of OsNMD3(ΔNLS) affected ribosome biogenesis and certain basic pathways, leading to pleiotropic abnormalities in plant growth. Taken together, these results strongly suggest that OsNMD3 is important for ribosome assembly and the maintenance of normal protein synthesis efficiency.

  17. Low intensity-ultrasonic irradiation for highly efficient, eco-friendly and fast synthesis of graphene oxide.

    PubMed

    Soltani, Tayyebeh; Lee, Byeong-Kyu

    2016-08-20

    High quality graphene oxide (GO) with low layer number (less than five layers) and large inter-layer space was produced via a new and efficient method using environmentally friendly, fast and economic ultrasonic radiation. The ultrasonic method neither generated any toxic gas nor required any NaNO3, which have been the main drawbacks of the Hummers methods. The major obstacles of the recently reported improved Hummers method for GO synthesis, such as high reaction temperature (50°C) and long reaction time (12h), were successfully solved using a low intensity-ultrasonic bath for 45min at 30°C, which significantly reduced the reaction time and energy consumption for GO synthesis. Furthermore, ultrasonic GO exhibited higher surface area, higher crystallinity and higher oxidation efficiency with many hydrophilic groups, fewer sheets with higher spaces between them, a higher sp(3)/sp(2) ratio, and more uniform size distribution than classically prepared GO. Therefore, the new ultrasonic method could be applicable for the sustainable and large-scale production of GO. The production yield of the ultrasonic-assisted GO was 1.25-fold greater than the GO synthesized with the improved Hummers method. Furthermore, the required production cost based on total energy consumption for ultrasonic GO was only 6.5% of that for classical GO.

  18. Green synthesis of polysaccharide/gold nanoparticle nanocomposite: an efficient ammonia sensor.

    PubMed

    Pandey, Sadanand; Goswami, Gopal K; Nanda, Karuna K

    2013-04-15

    A low cost eco-friendly method for the synthesis of gold nanoparticles (AuNPs) using guar gum (GG) as a reducing agent is reported. The nanoparticles obtained are characterized by UV-vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Based on these results, a potential mechanism for this method of AuNPs synthesis is discussed. GG/AuNPs nanocomposite (GG/AuNPs NC) was exploited for optical sensor for detection of aqueous ammonia based on surface plasmon resonance (SPR). It was found to have good reproducibility, response times of ∼10 s and excellent sensitivity with a detection limit of 1ppb (parts-per-billion). This system allows the rapid production of an ultra-low-cost GG/AuNPs NC-based aqueous ammonia sensor.

  19. Efficient One-Pot Synthesis of Colloidal Zirconium Oxide Nanoparticles for High-Refractive-Index Nanocomposites.

    PubMed

    Liu, Chao; Hajagos, Tibor Jacob; Chen, Dustin; Chen, Yi; Kishpaugh, David; Pei, Qibing

    2016-02-01

    Zirconium oxide nanoparticles are promising candidates for optical engineering, photocatalysis, and high-κ dielectrics. However, reported synthetic methods for the colloidal zirconium oxide nanoparticles use unstable alkoxide precursors and have various other drawbacks, limiting their wide application. Here, we report a facile one-pot method for the synthesis of colloidally stable zirconium oxide nanoparticles. Using a simple solution of zirconium trifluoroacetate in oleylamine, highly stable zirconium oxide nanoparticles have been synthesized with high yield, following a proposed amidization-assisted sol-gel mechanism. The nanoparticles can be readily dispersed in nonpolar solvents, forming a long-term stable transparent solution, which can be further used to fabricate high-refractive-index nanocomposites in both monolith and thin-film forms. In addition, the same method has also been extended to the synthesis of titanium oxide nanoparticles, demonstrating its general applicability to all group IVB metal oxide nanoparticles.

  20. Pd/Cu cooperative catalysis: an efficient synthesis of (3-isoindazolyl)allenes via cross-coupling of 2-alkynyl azobenzenes and terminal alkynes.

    PubMed

    Zhu, Chuan; Feng, Chao; Yamane, Motoki

    2017-02-23

    An efficient synthesis of (3-isoindazolyl)allenes from 2-alkynyl azobenzenes and terminal alkynes via cooperative Pd(PPh3)2Cl2/CuI-catalyzed cross-coupling has been developed. By making use of this approach, (3-isoindazolyl)allenes with various substituents can be synthesized in good to excellent yields. A rapid synthesis of biologically active indazolo[2,3-a]quinoline was also achieved using this method as the key step.

  1. Templated synthesis of nickel nanoparticles: Toward heterostructured nanocomposites for efficient hydrogen storage

    SciTech Connect

    Nelson, Nicholas Cole

    2013-01-01

    The world is currently facing an energy and environmental crisis for which new technologies are needed. Development of cost-competitive materials for catalysis and hydrogen storage on-board motor vehicles is crucial to lead subsequent generations into a more sustainable and energy independent future. This thesis presents work toward the scalable synthesis of bimetallic heterostructures that can enable hydrogen to compete with carbonaceous fuels by meeting the necessary gravimetric and volumetric energy densities and by enhancing hydrogen sorption/desorption kinetics near ambient temperatures and pressures. Utilizing the well-known phenomenon of hydrogen spillover, these bimetallic heterostructures could work by lowering the activation energy for hydrogenation and dehydrogenation of metals. Herein, we report a novel method for the scalable synthesis of silica templated zero-valent nickel particles (Ni⊂SiO2) that hold promise for the synthesis of nickel nanorods for use in bimetallic heterostructures for hydrogen storage. Our synthesis proceeds by chemical reduction of a nickel-hydrazine complex with sodium borohydride followed by calcination under hydrogen gas to yield silica encapsulated nickel particles. Transmission electron microscopy and powder X-ray diffraction were used to characterize the general morphology of the resultant nanocapsules as well as the crystalline phases of the incorporated Ni0 nanocrystals. The structures display strong magnetic behavior at room temperature and preliminary data suggests nickel particle size can be controlled by varying the amount of nickel precursor used in the synthesis. Calcination under different environments and TEM analysis provides evidence for an atomic migration mechanism of particle formation. Ni⊂SiO2 nanocapsules were used as seeds to induce heterogeneous nucleation and subsequent growth within the nanocapsule via electroless nickel plating. Nickel nanoparticle growth occurs

  2. Templated synthesis of nickel nanoparticles: Toward heterostructured nanocomposites for efficient hydrogen storage

    NASA Astrophysics Data System (ADS)

    Nelson, Nicholas Cole

    The world is currently facing an energy and environmental crisis for which new technologies are needed. Development of cost-competitive materials for catalysis and hydrogen storage on-board motor vehicles is crucial to lead subsequent generations into a more sustainable and energy independent future. This thesis presents work toward the scalable synthesis of bimetallic heterostructures that can enable hydrogen to compete with carbonaceous fuels by meeting the necessary gravimetric and volumetric energy densities and by enhancing hydrogen sorption/desorption kinetics near ambient temperatures and pressures. Utilizing the well-known phenomenon of hydrogen spillover, these bimetallic heterostructures could work by lowering the activation energy for hydrogenation and dehydrogenation of metals. Herein, we report a novel method for the scalable synthesis of silica templated zero-valent nickel particles (Ni⊂SiO2) that hold promise for the synthesis of nickel nanorods for use in bimetallic heterostructures for hydrogen storage. Our synthesis proceeds by chemical reduction of a nickel-hydrazine complex with sodium borohydride followed by calcination under hydrogen gas to yield silica encapsulated nickel particles. Transmission electron microscopy and powder X-ray diffraction were used to characterize the general morphology of the resultant nanocapsules as well as the crystalline phases of the incorporated Ni0 nanocrystals. The structures display strong magnetic behavior at room temperature and preliminary data suggests nickel particle size can be controlled by varying the amount of nickel precursor used in the synthesis. Calcination under different environments and TEM analysis provides evidence for an atomic migration mechanism of particle formation. Ni⊂SiO2 nanocapsules were used as seeds to induce heterogeneous nucleation and subsequent growth within the nanocapsule via electroless nickel plating. Nickel nanoparticle growth occurs under high temperature alkaline

  3. Stereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: a quantitative model.

    PubMed Central

    Schulz, T.; Pleiss, J.; Schmid, R. D.

    2000-01-01

    The lipase from Pseudomonas cepacia represents a widely applied catalyst for highly enantioselective resolution of chiral secondary alcohols. While its stereopreference is determined predominantly by the substrate structure, stereoselectivity depends on atomic details of interactions between substrate and lipase. Thirty secondary alcohols with published E values using P. cepacia lipase in hydrolysis or esterification reactions were selected, and models of their octanoic acid esters were docked to the open conformation of P. cepacia lipase. The two enantiomers of 27 substrates bound preferentially in either of two binding modes: the fast-reacting enantiomer in a productive mode and the slow-reacting enantiomer in a nonproductive mode. Nonproductive mode of fast-reacting enantiomers was prohibited by repulsive interactions. For the slow-reacting enantiomers in the productive binding mode, the substrate pushes the active site histidine away from its proper orientation, and the distance d(H(N epsilon) - O(alc)) between the histidine side chain and the alcohol oxygen increases, d(H(N epsilon) - O(alc)) was correlated to experimentally observed enantioselectivity: in substrates for which P. cepacia lipase has high enantioselectivity (E > 100), d(H(N epsilon) - O(alc)) is >2.2 A for slow-reacting enantiomers, thus preventing efficient catalysis of this enantiomer. In substrates of low enantioselectivity (E < 20), the distance d(H(N epsilon) - O(alc)) is less than 2.0 A, and slow- and fast-reacting enantiomers are catalyzed at similar rates. For substrates of medium enantioselectivity (20 < E < 100), d(H(N epsilon) - O(alc)) is around 2.1 A. This simple model can be applied to predict enantioselectivity of P. cepacia lipase toward a broad range of secondary alcohols. PMID:10892799

  4. Total Synthesis of (+)-Superstolide A

    PubMed Central

    Tortosa, Mariola; Yakelis, Neal A.; Roush, William R.

    2009-01-01

    A convergent and highly stereocontrolled total synthesis of the cytotoxic macrolide (+)-superstolide A is described. Key features of this synthesis include the use of bimetallic linchpin 36b for uniting the C(1)-C(15) (43) and the C(20)-C(27) (38) fragments of the natural product, a late-stage Suzuki macrocyclization of 49, and a highly diastereoselective transannular Diels-Alder reaction of macrocyclic octanene 4. In contrast, the intramolecular Diels-Alder reaction of pentaenal 5 provided the desired cycloadduct with lower stereoselectivity (6:1:1). PMID:18956845

  5. Highly Regio- and Stereoselective Diels-Alder Cycloadditions via Two-Step and Multicomponent Reactions Promoted by Infrared Irradiation under Solvent-Free Conditions

    PubMed Central

    Flores-Conde, Maria Ines; Reyes, Leonor; Herrera, Rafael; Rios, Hulme; Vazquez, Miguel A.; Miranda, Rene; Tamariz, Joaquin; Delgado, Francisco

    2012-01-01

    Infrared irradiation promoted the Diels-Alder cycloadditions of exo-2-oxazolidinone dienes 1–3 with the Knoevenagel adducts 4–6, as dienophiles, leading to the synthesis of new 3,5-diphenyltetrahydrobenzo[d]oxazol-2-one derivatives (7, 9, 11 and 13–17), under solvent-free conditions. These cycloadditions were performed with good regio- and stereoselectivity, favoring the para-endo cycloadducts. We also evaluated the one-pot three-component reaction of active methylene compounds 20, benzaldehydes 21 and exo-2-oxazolidinone diene 2 under the same reaction conditions. A cascade Knoevenagel condensation/Diels-Alder cycloaddition reaction was observed, resulting in the final adducts 13–16 in similar yields. These procedures are environmentally benign, because no solvent and no catalyst were employed in these processes. The regioselectivity of these reactions was rationalized by Frontier Molecular Orbital (FMO) calculations. PMID:22489113

  6. Miniaturization of metal-biomolecule frameworks based on stereoselective self-assembly and potential application in water treatment and as antibacterial agents.

    PubMed

    Pu, Fang; Liu, Xia; Xu, Bailu; Ren, Jinsong; Qu, Xiaogang

    2012-04-02

    Miniaturization of metal-biomolecule frameworks (MBioFs) to the nanometer scale represents a novel strategy for fabricating materials with tunable physical and chemical properties. Herein, we demonstrate a simple, low-cost, and completely organic solvent-free strategy for constructing a dl-glutamic acid-copper ion-based three-dimensional nanofibrous network structure. The building blocks used are available in large quantities and do not require any laborious synthesis or modification. Importantly, we demonstrate with an intriguing example, that the self-assembly ability of supramolecular nanofibers could be finely tuned with the ligands' chirality. This offers opportunities for obtaining one-dimensional hierarchical nanostructures and expands the investigation scope of stereoselective self-assembly. Furthermore, the material displays good ability in removing anionic dyes from water and inhibits the growth of both Gram positive and Gram negative bacteria, possibly through the contact-killing mechanism; this indicates potential applications in environmental issues and antimicrobial nanotherapeutics.

  7. A novel and efficient samarium iodide-mediated synthesis of neoflavonoids (4-arycloumarins)

    SciTech Connect

    Nagasawa, Kazuo; Ryohke, Hirosi; Ohnishi, Makoto; Ito, Keiichi

    1995-12-31

    Bioactive 4-arylcoumarins (4-aryl-2H-1-benzopyran-2-ones) have been recently isolated from the plants belonging to the families like Leguminosae, Guttiferae, and Compositae, some of which are still used as the traditional folk medicine. Despite many methods reported so far, there appears to be of limited success or of no success in some cases (II{sub b-g}) and, therefore, a simpler and more reliable one remains to be highly desired. Thus, a new and sterling protocol is now presented for the synthesis of neoflavonoids, which involves the intramolecular Reformatsky-type reaction via a one electron transfer process with samarium diiodide as a key step.

  8. One pot, rapid and efficient synthesis of water dispersible gold nanoparticles using alpha-amino acids

    NASA Astrophysics Data System (ADS)

    Wangoo, Nishima; Kaur, Sarabjit; Bajaj, Manish; Jain, D. V. S.; Sharma, Rohit K.

    2014-10-01

    A detailed study on the synthesis of spherical and monodispersed gold nanoparticles (AuNPs) using all of the 20 naturally occurring α-amino acids has been reported. The synthesized nanoparticles have been further characterized using various techniques such as absorbance spectroscopy, transmission electron microscopy, dynamic light scattering and nuclear magnetic resonance. Size control of the nanoparticles has been achieved by varying the ratio of the gold ion to the amino acid. These monodispersed water soluble AuNPs synthesized using non-toxic, naturally occurring α-amino acids as reducing and capping/stabilizing agents serve as a remarkable example of green chemistry.

  9. Simple, general, and efficient synthesis of meso-substituted borondipyrromethenes from a single platform.

    PubMed

    Peña-Cabrera, Eduardo; Aguilar-Aguilar, Angélica; Gonzalez-Domínguez, Martha; Lager, Erik; Zamudio-Vazquez, Rubí; Godoy-Vargas, Jazmín; Villanueva-García, Fabian

    2007-09-27

    An unprecedented synthesis of 8-substituted-borondipyrromethenes is described starting from 8-thiomethylbodipy 1. Aryl, heteroaryl, alkenyl, and organometallic boronic acids smoothly reacted with 1 in the presence of a catalytic amount of Pd(0) and a stoichiometric amount of Cu(I)-2-thienylcarboxylate under neutral conditions to give the corresponding Bodipy analogues in good to quantitative yields (20 examples). A remarkable reactivity was observed in some cases, e.g., ferrocenylboronic acid gave the product in 98% isolated yield after only 10 min at 55 degrees C.

  10. Stereoselectivity in bioaccumulation and excretion of epoxiconazole by mealworm beetle (Tenebrio molitor) larvae.

    PubMed

    Lv, Xiaotian; Liu, Chen; Li, Yaobin; Gao, Yongxin; Wang, Huili; Li, Jianzhong; Guo, Baoyuan

    2014-09-01

    Stereoselectivity in bioaccumulation and excretion of stereoisomers of epoxiconazole by mealworm beetle (Tenebrio molitor) larvae through dietary exposure was investigated. Liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method that use a ChiralcelOD-3R[cellulosetris-Tris-(3, 5-dichlorophenyl-carbamate)] chromatography column was applied to carry out chiral separation of the stereoisomers. Wheat bran was spiked with racemic epoxiconazole at two dose levels of 20mg/kg and 2mg/kg (dry weight) to feed T. molitor larvae. The results showed that both the doses of epoxiconazole were taken up by Tenebrio molitor larvae rapidly at the initial stages. There was a significant trend of stereoselective bioaccumulation in the larvae with a preferential accumulation of (-)-epoxiconazole in the 20mg/kg dose. The stereoselectivity in bioaccumulation in the 2mg/kg dosage was not obvious compared to the 20mg/kg group. Results of excretion indicated an active excretion is an important pathway for the larvae to eliminate epoxiconazole which was a passive transport process with non stereoselectivity. The faster elimination might be the reason for the low accumulation of epoxiconazole, as measured by bioaccumulation factor (BAF).

  11. Supramolecular catalysis with extended aggregates and gels: inversion of stereoselectivity caused by self-assembly.

    PubMed

    Rodríguez-Llansola, Francisco; Miravet, Juan F; Escuder, Beatriu

    2010-07-26

    L-Proline-L-valine dipeptide derivatives, which self-assemble in toluene, have been studied as stereoselective catalysts in the conjugate addition of cyclohexanone to trans-beta-nitrostyrene. Remarkable effects on the stereoselectivity are observed associated to the aggregation of the catalyst. Outstanding differences were observed between the catalytic activity of compound 1, which forms supramolecular gels in toluene, and compound 2, which is not a gelator. In the former case, the enantioselectivity of the reaction was almost insensitive to changes in catalyst concentration and temperature, but in the case of compound 2, the catalytic activity was very much affected by those variables. Structural studies indicate that the results can be rationalized by taking into account significant conformational changes experienced by the catalytic L-proline derivatives associated with the aggregation process. The results highlight that catalyst self-assembly is a very important issue to consider in the stereoselective outcome of organocatalytic reactions. Especially relevant is the fact that the use of supramolecular gels as organocatalysts emerges as a technique that affords reliable and constant stereoselectivity in different conditions with the added value of easy catalyst recovery.

  12. Influence of Uptake Pathways on the Stereoselective Dissipation of Chiral Neonicotinoid Sulfoxaflor in Greenhouse Vegetables.

    PubMed

    Chen, Zenglong; Dong, Fengshou; Pan, Xinglu; Xu, Jun; Liu, Xingang; Wu, Xiaohu; Zheng, Yongquan

    2016-04-06

    Stereoselectivity is of vital importance in our environment and needs to be taken into account for comprehensive risk assessment and regulatory decisions of chiral neonicotinoid sulfoxaflor. However, little is known about the dissipation of sulfoxaflor stereoisomers with respect to stereoselectivity in plants under greenhouse cultivation. To bridge the knowledge gap, the current study was initiated to investigate the stereoselective degradation of sulfoxaflor in solar greenhouse cucumber and tomato from foliage and root uptake pathways. The stereoselective dissipation of sulfoxaflor was not statistically different between enantiomer pairs from foliage and root pathways of vegetables (P < 0.05). The persistence of sulfoxaflor stereoisomers was consistently prolonged under the foliage uptake pathway (t1/2, 3.38-14.09 days) compared to the root uptake pathway (t1/2, 2.65-5.07 days) in both vegetable fruits. Nevertheless, the concentrations of (+)-sulfoxaflor A and (-)-sulfoxaflor B were both slightly higher than that of their antipode. The tiny difference should be emphasized because it might be magnified to a significant difference by the high-potential bioaccumulation of sulfoxaflor in the food chain.

  13. Applying Symmetries of Common Objects to Help Students Understand Stereoselectivity for Apparently Symmetric Substrates

    ERIC Educational Resources Information Center

    Jittam, Piyachat; Ruenwongsa, Pintip; Panijpan, Bhinyo

    2008-01-01

    We have found it an effective way of teaching symmetry in the context of stereoselectivity, to use common everyday objects with the same point groups as the substrates involved. This has helped students to distinguish between those symmetry elements which allow for stereospecificity and those which preclude it. Two symmetry elements, the simple…

  14. Stereoselective Access to Tubuphenylalanine and Tubuvaline: Improved Mn-Mediated Radical Additions and Assembly of A Tubulysin Tetrapeptide Analog

    PubMed Central

    Banerjee, Koushik; Marié, Jean-Charles; Mali, Umesh; Yao, Lei

    2016-01-01

    Synthesis of tubuphenylalanine and tubuvaline, α-substituted γ-amino acid building blocks for tubulysin family of antimitotic compounds, has been improved using a radical addition reaction in the presence of unprotected hydroxyl functionality. The key carbon–carbon bond construction entails stereoselective Mn-mediated photolytic additions of alkyl iodides to the C=N bond of chiral N-acylhydrazones, and generates the chiral amines in high yield with complete stereocontrol. Reductive N–N bond cleavage and alcohol oxidation converted these amino alcohols into the corresponding γ-amino acids. The route to tubuvaline proceeded via peptide coupling with serine methyl ester, followed by a high-yielding sequence to convert the serine amide to a thiazole. Finally, peptide bond construction established the tubulysin framework in the form of a C-terminal alcohol analog. Attempted oxidation to the C-terminal carboxylate was unsuccessful; control experiments with dipeptide 18 showed a cyclization interfered with the desired oxidation process. PMID:26883395

  15. KF/Clinoptilolite: an efficient promoter for the synthesis of thioethers.

    PubMed

    Salmanpour, Sadegh; Khalilzadeh, Mohammad A; Hosseini, Abolfazl

    2013-06-01

    Potassium fluoride impregnated on natural zeolite as a new solid base system effectively catalyzes the coupling of thiophenols with electron-deficient fluoro-, chloro- and bromo-arenes in DMSO. This versatile and efficient solid base has been demonstrated to afford the corresponding desired products in good to excellent yields. This procedure provides a convenient, efficient and practical method for the preparation of diaryl thioethers.

  16. Spray-combustion synthesis: efficient solution route to high-performance oxide transistors.

    PubMed

    Yu, Xinge; Smith, Jeremy; Zhou, Nanjia; Zeng, Li; Guo, Peijun; Xia, Yu; Alvarez, Ana; Aghion, Stefano; Lin, Hui; Yu, Junsheng; Chang, Robert P H; Bedzyk, Michael J; Ferragut, Rafael; Marks, Tobin J; Facchetti, Antonio

    2015-03-17

    Metal-oxide (MO) semiconductors have emerged as enabling materials for next generation thin-film electronics owing to their high carrier mobilities, even in the amorphous state, large-area uniformity, low cost, and optical transparency, which are applicable to flat-panel displays, flexible circuitry, and photovoltaic cells. Impressive progress in solution-processed MO electronics has been achieved using methodologies such as sol gel, deep-UV irradiation, preformed nanostructures, and combustion synthesis. Nevertheless, because of incomplete lattice condensation and film densification, high-quality solution-processed MO films having technologically relevant thicknesses achievable in a single step have yet to be shown. Here, we report a low-temperature, thickness-controlled coating process to create high-performance, solution-processed MO electronics: spray-combustion synthesis (SCS). We also report for the first time, to our knowledge, indium-gallium-zinc-oxide (IGZO) transistors having densification, nanoporosity, electron mobility, trap densities, bias stability, and film transport approaching those of sputtered films and compatible with conventional fabrication (FAB) operations.

  17. Efficient Synthesis of Nicotinamide-1-15N for Ultrafast NMR Hyperpolarization Using Parahydrogen

    PubMed Central

    2016-01-01

    Nicotinamide (a vitamin B3 amide) is one of the key vitamins as well as a drug for treatment of M. tuberculosis, HIV, cancer, and other diseases. Here, an improved Zincke reaction methodology is presented allowing for straightforward and scalable synthesis of nicotinamide-1-15N with an excellent isotopic purity (98%) and good yield (55%). 15N nuclear spin label in nicotinamide-1-15N can be NMR hyperpolarized in seconds using parahydrogen gas. NMR hyperpolarization using the process of temporary conjugation between parahydrogen and to-be-hyperpolarized biomolecule on hexacoordinate iridium complex via the Signal Amplification By Reversible Exchange (SABRE) method significantly increases detection sensitivity (e.g., >20 000-fold for nicotinamide-1-15N at 9.4 T) as has been shown by Theis T. et al. (J. Am. Chem. Soc.2015, 137, 1404), and hyperpolarized in this fashion, nicotinamide-1-15N can be potentially used to probe metabolic processes in vivo in future studies. Moreover, the presented synthetic methodology utilizes mild reaction conditions, and therefore can also be potentially applied to synthesis of a wide range of 15N-enriched N-heterocycles that can be used as hyperpolarized contrast agents for future in vivo molecular imaging studies. PMID:26999571

  18. Spray-combustion synthesis: Efficient solution route to high-performance oxide transistors

    PubMed Central

    Yu, Xinge; Smith, Jeremy; Zhou, Nanjia; Zeng, Li; Guo, Peijun; Xia, Yu; Alvarez, Ana; Aghion, Stefano; Lin, Hui; Yu, Junsheng; Chang, Robert P. H.; Bedzyk, Michael J.; Ferragut, Rafael; Marks, Tobin J.; Facchetti, Antonio

    2015-01-01

    Metal-oxide (MO) semiconductors have emerged as enabling materials for next generation thin-film electronics owing to their high carrier mobilities, even in the amorphous state, large-area uniformity, low cost, and optical transparency, which are applicable to flat-panel displays, flexible circuitry, and photovoltaic cells. Impressive progress in solution-processed MO electronics has been achieved using methodologies such as sol gel, deep-UV irradiation, preformed nanostructures, and combustion synthesis. Nevertheless, because of incomplete lattice condensation and film densification, high-quality solution-processed MO films having technologically relevant thicknesses achievable in a single step have yet to be shown. Here, we report a low-temperature, thickness-controlled coating process to create high-performance, solution-processed MO electronics: spray-combustion synthesis (SCS). We also report for the first time, to our knowledge, indium-gallium-zinc-oxide (IGZO) transistors having densification, nanoporosity, electron mobility, trap densities, bias stability, and film transport approaching those of sputtered films and compatible with conventional fabrication (FAB) operations. PMID:25733848

  19. Synthesis of amino-rich silica-coated magnetic nanoparticles for the efficient capture of DNA for PCR.

    PubMed

    Bai, Yalong; Cui, Yan; Paoli, George C; Shi, Chunlei; Wang, Dapeng; Zhou, Min; Zhang, Lida; Shi, Xianming

    2016-09-01

    Magnetic separation has great advantages over traditional bio-separation methods and has become popular in the development of methods for the detection of bacterial pathogens, viruses, and transgenic crops. Functionalization of magnetic nanoparticles is a key factor for efficient capture of the target analytes. In this paper, we report the synthesis of amino-rich silica-coated magnetic nanoparticles using a one-pot method. This type of magnetic nanoparticle has a rough surface and a higher density of amino groups than the nanoparticles prepared by a post-modification method. Furthermore, the results of hydrochloric acid treatment indicated that the magnetic nanoparticles were stably coated. The developed amino-rich silica-coated magnetic nanoparticles were used to directly adsorb DNA. After magnetic separation and blocking, the magnetic nanoparticles and DNA complexes were used directly for the polymerase chain reaction (PCR), without onerous and time-consuming purification and elution steps. The results of real-time quantitative PCR showed that the nanoparticles with higher amino group density resulted in improved DNA capture efficiency. The results suggest that amino-rich silica-coated magnetic nanoparticles are of great potential for efficient bio-separation of DNA prior to detection by PCR.

  20. Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation

    PubMed Central

    KAWASHIMA, NAGAKO; QU, HUANHUAN; LOBATON, MARLIN; ZHU, ZHENYUAN; SOLLOGOUB, MATTHIEU; CAVENEE, WEBSTER K.; HANDA, KAZUKO; HAKOMORI, SEN-ITIROH; ZHANG, YONGMIN

    2014-01-01

    Glycosphingolipids are components of essentially all mammalian cell membranes and are involved in a variety of significant cellular functions, including proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide (GM3) is known to inhibit the activation of epidermal growth factor receptor (EGFR). In the present study, an efficient method for the total chemical synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3 was developed. The structures of the synthesized compounds were fully characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In analyses of EGFR autophosphorylation and cell proliferation ([3H]-thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro-derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity. Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory effect on ΔEGFR, a splicing variant of EGFR that lacks exons 2–7 and is often found in human glioblastomas. The chemical synthesis of other GM3 derivatives using approaches similar to those described in the present study, has the potential to create more potent EGFR inhibitors to block cell growth or motility of a variety of types of cancer that express either wild-type EGFR or ΔEGFR. PMID:24944646

  1. Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation.

    PubMed

    Kawashima, Nagako; Qu, Huanhuan; Lobaton, Marlin; Zhu, Zhenyuan; Sollogoub, Matthieu; Cavenee, Webster K; Handa, Kazuko; Hakomori, Sen-Itiroh; Zhang, Yongmin

    2014-04-01

    Glycosphingolipids are components of essentially all mammalian cell membranes and are involved in a variety of significant cellular functions, including proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide (GM3) is known to inhibit the activation of epidermal growth factor receptor (EGFR). In the present study, an efficient method for the total chemical synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3 was developed. The structures of the synthesized compounds were fully characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In analyses of EGFR autophosphorylation and cell proliferation ([(3)H]-thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro-derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity. Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory effect on ΔEGFR, a splicing variant of EGFR that lacks exons 2-7 and is often found in human glioblastomas. The chemical synthesis of other GM3 derivatives using approaches similar to those described in the present study, has the potential to create more potent EGFR inhibitors to block cell growth or motility of a variety of types of cancer that express either wild-type EGFR or ΔEGFR.

  2. Efficient synthesis of the intermediate of abacavir and carbovir using a novel (+)-γ-lactamase as a catalyst.

    PubMed

    Gao, Shuaihua; Zhu, Shaozhou; Huang, Rong; Lu, Yingxiu; Zheng, Guojun

    2015-09-15

    The enantiomers of 2-azabicyclo[2.2.1]hept-5-en-3-one (γ-lactam) are key chiral synthons in the synthesis of antiviral drugs such as carbovir and abacavir. (+)-γ-Lactamase can be used as a catalyst in the enzymatic preparation of optically pure (-)-γ-lactam. Here, a (+)-γ-lactamase discovered from Bradyrhizobium japonicum USDA 6 by sequence-structure guided genome mining was cloned, purified and characterized. The enzyme possesses a significant catalytic activity towards γ-lactam. The active site of the (+)-γ-lactamase was studied by homologous modeling and molecular docking, and the accuracy of the prediction was confirmed by site-specific mutagenesis. The (+)-γ-lactamase reveals the great practical potential as an enzymatic method for the efficient production of carbocyclic nucleosides of pharmaceutical interest.

  3. Synthesis of TiO2 microspheres building on the etherification and its application for high efficiency solar cells

    NASA Astrophysics Data System (ADS)

    Liu, Shi-Dong; Ren, Ying-Ke; Zhou, Zheng; Chen, Wang-Chao; Li, Zhao-Qian; Guo, Fu-Ling; Mo, Li-E.; Wu, Ji-Huai; Hu, Lin-Hua; Dai, Song-Yuan

    2016-10-01

    This paper describes a facile solvothermal method to synthesize TiO2 microspheres by employing ethylene glycol monomethyl ether and ethylene glycol as solvent. By analyzing the resulted supernatant after reaction, it was proved that the etherification reaction of glycol monomethyl ether and the ligand exchange between ethylene glycol and tetra-n-butyl titanate played a key role in synthesis of TiO2 microspheres. These as-obtained TiO2 microspheres exhibited high specific surface area up to 113.24 m2 g-1 and have a narrow pore size distribution (6.94 nm). When applied to the photoanode, the TiO2 microsphere-based dye-sensitized solar cells achieved a high power conversion efficiency up to 10.25%.

  4. Efficient utilization of greenhouse gases in a gas-to-liquids process combined with CO2/steam-mixed reforming and Fe-based Fischer-Tropsch synthesis.

    PubMed

    Zhang, Chundong; Jun, Ki-Won; Ha, Kyoung-Su; Lee, Yun-Jo; Kang, Seok Chang

    2014-07-15

    Two process models for carbon dioxide utilized gas-to-liquids (GTL) process (CUGP) mainly producing light olefins and Fischer-Tropsch (F-T) synthetic oils were developed by Aspen Plus software. Both models are mainly composed of a reforming unit, an F-T synthesis unit and a recycle unit, while the main difference is the feeding point of fresh CO2. In the reforming unit, CO2 reforming and steam reforming of methane are combined together to produce syngas in flexible composition. Meanwhile, CO2 hydrogenation is conducted via reverse water gas shift on the Fe-based catalysts in the F-T synthesis unit to produce hydrocarbons. After F-T synthesis, the unreacted syngas is recycled to F-T synthesis and reforming units to enhance process efficiency. From the simulation results, it was found that the carbon efficiencies of both CUGP options were successfully improved, and total CO2 emissions were significantly reduced, compared with the conventional GTL processes. The process efficiency was sensitive to recycle ratio and more recycle seemed to be beneficial for improving process efficiency and reducing CO2 emission. However, the process efficiency was rather insensitive to split ratio (recycle to reforming unit/total recycle), and the optimum split ratio was determined to be zero.

  5. Growth rate hypothesis and efficiency of protein synthesis under different sulphate concentrations in two green algae.

    PubMed

    Giordano, Mario; Palmucci, Matteo; Raven, John A

    2015-11-01

    The growth rate hypothesis (GRH) predicts a positive correlation between growth rate and RNA content because growth depends upon the protein synthesis machinery. The application of this hypothesis to photoautotrophic organisms has been questioned. We tested the GRH on one prasinophycean, Tetraselmis suecica, and one chlorophycean, Dunaliella salina, grown at three sulphate concentrations. Sulphate was chosen because its concentration in the oceans increased through geological time and apparently had a role in the evolutionary trajectories of phytoplankton. Cell protein content and P quota were positively related to the RNA content (r = 0.62 and r = 0.74, respectively). The correlation of the RNA content with growth rates (r = 0.95) indicates that the GRH was valid for these species when growth rates were below 0.82 d(-1) .

  6. Synthesis of homogeneous Pt-bimetallic nanoparticles as highly efficient electrocatalysts.

    SciTech Connect

    Wang, C.; Chi, M.; Li, D.; van der Vliet, D.; Wang, G.; Lin, Q.; Mitchell, J.; More, K. L.; Markovic, N. M.; Stamenkovic, V. R.

    2011-01-01

    Alloying has shown enormous potential for tailoring the atomic and electronic structures, and improving the performance of catalytic materials. Systematic studies of alloy catalysts are, however, often compromised by inhomogeneous distribution of alloying components. Here we introduce a general approach for the synthesis of monodispersed and highly homogeneous Pt-bimetallic alloy nanocatalysts. Pt{sub 3}M (where M = Fe, Ni, or Co) nanoparticles were prepared by an organic solvothermal method and then supported on high surface area carbon. These catalysts attained a homogeneous distribution of elements, as demonstrated by atomic-scale elemental analysis using scanning transmission electron microscopy. They also exhibited high catalytic activities for the oxygen reduction reaction (ORR), with improvement factors of 2-3 versus conventional Pt/carbon catalysts. The measured ORR catalytic activities for Pt{sub 3}M nanocatalysts validated the volcano curve established on extended surfaces, with Pt{sub 3}Co being the most active alloy.

  7. Fast and efficient MCR-based synthesis of clickable rhodamine tags for protein profiling.

    PubMed

    Brauch, Sebastian; Henze, Michael; Osswald, Bianca; Naumann, Kai; Wessjohann, Ludger A; van Berkel, Sander S; Westermann, Bernhard

    2012-02-07

    Protein profiling probes are important tools for studying the composition of the proteome and as such have contributed greatly to the understanding of various complex biological processes in higher organisms. For this purpose the application of fluorescently labeled activity or affinity probes is highly desirable. Especially for in vivo detection of low abundant target proteins, otherwise difficult to analyse by standard blotting techniques, fluorescently labeled profiling probes are of high value. Here, a one-pot protocol for the synthesis of activated fluorescent labels (i.e. azide, alkynyl or NHS), based on the Ugi-4-component reaction (Ugi-4CR), is presented. As a result of the peptoidic structure formed, the fluorescent properties of the products are pH insensitive. Moreover, the applicability of these probes, as exemplified by the labeling of model protein BSA, will be discussed.

  8. An efficient green synthesis of 2-arylbenzothiazole analogues as potent antibacterial and anticancer agents.

    PubMed

    Chhabra, Mohit; Sinha, Sohini; Banerjee, Swagata; Paira, Priyankar

    2016-01-01

    We have demonstrated a novel and green approach for the synthesis of 2-substituted benzothiazole analogues. A number of 2-aryl and heteroaryl benzothiazole scaffolds were synthesized using Amberlite IR-120 resin under microwave irradiation. The catalytic role and reusability of the resin was well established here. 2-Substituted benzothiazole analogues (3a-l) were also tested against several bacterial strains (Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella) and cancer cell lines (MCF-7 and HeLa). The stability of compound 2-phenyl benzothiazole (3a) and 2-pyridin-2-yl-benzothiazole (3k) in GSH (0.01mM dissolved in DMSO) was measured by UV-Vis spectroscopy. Compound 3k also shows remarkable fluorescence in MeOH.

  9. Efficient Synthesis of Dimethyl Ether from Methanol in a Bifunctional Zeolite Membrane Reactor.

    PubMed

    Zhou, Chen; Wang, Nanyi; Qian, Yanan; Liu, Xiaoxing; Caro, Jürgen; Huang, Aisheng

    2016-10-04

    A sandwich FAU-LTA zeolite dual-layer membrane has been developed and used as a catalytic membrane reactor for the synthesis of dimethyl ether (DME). In the top H-FAU layer with mild acidity, methanol is dehydrated to DME. The other reaction product, water, is removed in situ through a hydrophilic Na-LTA layer, which is located between the porous alumina support and the H-FAU top layer. The combination of mild acidity with the continuous removal of water results in high methanol conversion (90.9 % at 310 °C) and essentially 100 % DME selectivity. Furthermore, owing to the selective and continuous removal of water through the Na-LTA membrane, catalyst deactivation can be effectively suppressed.

  10. Synthesis of dye-sensitized solar cells. Efficiency cells as a thickness of titanium dioxide

    NASA Astrophysics Data System (ADS)

    Szura, Dominika

    2016-12-01

    Defying the influence of the thickness of TiO2 efficiency of dye-sensitized solar cell. It was confirmed that the compatibility of printed layers with the parameters closely related with the DSSC. It was found that the increase in thickness of the titanium dioxide layer, increases the distance between the electrodes, determined by the thickness of the Surlyn foil. With the rise of thickness of dyed layer of TiO2 established decrease in the value of its transmittance. Greatest transparency and aesthetic value obtained for photovoltaic modules with a single layer of titanium dioxide. The improved performance efficiency and preferred yields maximum power were noticed and exhibited by the cells covered with three layers of TiO2. It was established that the behaviour of economic efficiency in the production process, provides a range of cells with two layers of oxide, showing a similar performance and greater transparency.

  11. Efficient synthesis of a multi-substituted diphenylmethane skeleton as a steroid mimetic.

    PubMed

    Misawa, Takashi; Tanaka, Katsuya; Demizu, Yosuke; Kurihara, Masaaki

    2017-03-24

    Steroids are important components of cell membranes and are involved in several physiological functions. A diphenylmethane (DPM) skeleton has recently been suggested to act as a mimetic of the steroid skeleton. However, difficulties are associated with efficiently introducing different substituents between two phenyl rings of the DPM skeleton, and, thus, further structural development based on the DPM skeleton has been limited. We herein developed an efficient synthetic method for introducing different substituents into two phenyl rings of the DPM skeleton. We also synthesized DPM-based estrogen receptor (ER) modulators using our synthetic method and evaluated their ER transcriptional activities.

  12. Efficiency of cell-free protein synthesis based on a crude cell extract from Escherichia coli, wheat germ, and rabbit reticulocytes.

    PubMed

    Hino, Mami; Kataoka, Masatoshi; Kajimoto, Kazuaki; Yamamoto, Takenori; Kido, Jun-Ichi; Shinohara, Yasuo; Baba, Yoshinobu

    2008-01-20

    The efficiency of protein synthesis for glyceraldehyde-3-phosphate dehydrogenase (G3PDH) was examined with several in vitro coupled transcription/translation protein synthesis systems based on Escherichia coli lysate, wheat germ, or reticulocyte lysate, and an in vitro translation system based on wheat germ extract. A significant amount of protein synthesis was observed only in systems based on E. coli using pET/G3PDH as the expression vector. A remarkable increase of protein synthesis was obtained in wheat germ using a pT(N)T expression vector which contains a 5'-globin leader sequence and a synthetic poly(A)(30) tail instead of pET. A significant difference of T7 RNA polymerase presence by Western blot analysis was not observed in the first four systems, and the difference of total RNA presence in each reaction mixture by Northern blot analysis seemed unrelated to protein synthesis. Although a small amount of protein was synthesized using RNA-encoding G3PDH transcribed in vitro with pET/G3PDH by an in vitro translation system, an extreme increase was observed using transcribed RNA with pEU/G3PDH, which contains T7 RNA promoter and a translation enhancer, Omega sequence. These results suggest that the presence of an enhancer sequence for translation is one of the critical steps for protein synthesis by a eukaryotic cell-free protein synthesis system.

  13. An Efficient Synthesis of 5-Amido-3-Hydroxy-4-Pyrones as Inhibitors of Matrix Metalloproteinases

    PubMed Central

    Yan, Yi-Long; Cohen, Seth M.

    2008-01-01

    3-Hydroxy-4-pyrones are a class of important metal chelators with versatile medicinal applications. An efficient pathway for the preparation of new 5-amido-3-hydroxy-4-pyrone derivatives has been developed. The synthesized 5-amido-3-hydroxy-4-pyrones have been evaluated as inhibitors of matrix metalloproteinases. PMID:17521196

  14. Highly efficient synthesis of phenols by copper-catalyzed hydroxylation of aryl iodides, bromides, and chlorides.

    PubMed

    Yang, Kai; Li, Zheng; Wang, Zhaoyang; Yao, Zhiyi; Jiang, Sheng

    2011-08-19

    8-Hydroxyquinolin-N-oxide was found to be a very efficient ligand for the copper-catalyzed hydroxylation of aryl iodides, aryl bromides, or aryl chlorides under mild reaction conditions. This methodology provides a direct transformation of aryl halides to phenols and to alkyl aryl ethers. The inexpensive catalytic system showed great functional group tolerance and excellent selectivity.

  15. Efficient utilization of crude glycerol as fermentation substrate in the synthesis of poly(3-hydroxybutyrate) biopolymers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One refined and 2 crude glycerol samples were utilized to produce poly(3-hydroxybutyrate) (PHB) by Pseudomonas oleovorans NRRL B-14682. Fermentation conditions were determined to efficiently utilize glycerol while maintaining PHB yields. A batch culture protocol including 1% glycerol and an aerati...

  16. Solid-state synthesis of ZnO nanostructures for quasi-solid dye-sensitized solar cells with high efficiencies up to 6.46%.

    PubMed

    Shi, Yantao; Wang, Kai; Du, Yi; Zhang, Hong; Gu, Junfu; Zhu, Chao; Wang, Lin; Guo, Wei; Hagfeldt, Anders; Wang, Ning; Ma, Tingli

    2013-08-27

    Solid-state synthesis of ZnO nanostructured building blocks is presented in this work for the fabrication of high efficiency quasi-solid dye-sensitized solar cells (DSSCs). The sponge-like photoanode has high optical density and better connections. Baking the photoanode at low temperature, photoconversion efficiencies of up to 6.46% are yielded by the quasi-solid DSSCs. Furthermore, we demonstrate better stability of our ZnO quasi-solid DSSCs.

  17. Caesium fluoride-promoted Stille coupling reaction: an efficient synthesis of 9Z-retinoic acid and its analogues using a practical building block.

    PubMed

    Okitsu, Takashi; Iwatsuka, Kinya; Wada, Akimori

    2008-12-21

    A highly efficient and rapid total synthesis of 9Z-retinoic acid was accomplished by caesium fluoride-promoted Stille coupling reaction; using a common building block, 9Z-retinoic acid analogues were also prepared by the same method without isomerisation of the Z-double bond.

  18. Efficient traceless solid-phase synthesis of 3,4-dihydropyrazino[1,2-b]indazoles and their 6-oxides.

    PubMed

    Pudelová, Nadezda; Krchnák, Viktor

    2009-01-01

    A highly efficient novel traceless solid-phase synthesis of 3,4-dihydropyrazino[1,2-b]indazoles and their 6-oxides was developed by using commercially available building blocks, diamines, 2-nitrobenzenesulfonyl chlorides, and bromoketones/bromoacetates. Mild reaction conditions, diversely substituted building blocks, and high purity of crude products enabled effective combinatorial syntheses of libraries.

  19. Facile mesoporous template-assisted hydrothermal synthesis of ordered mesoporous magnesium silicate as an efficient adsorbent

    NASA Astrophysics Data System (ADS)

    Lu, Qingshan; Li, Qiang; Zhang, Jingjing; Li, Jingfeng; Lu, Jinhua

    2016-01-01

    Mesoporous materials with unique structure as well as special morphology have potential applications in pollutant adsorption. In this work, using mesoporous silica SBA-15 filled with carbon (C@SBA-15) as both silicon source and assisted template, the ordered mesoporous magnesium silicate (Mg3Si4O9(OH)4) has been fabricated at 140 °C by a novel and facile hydrothermal method. During the hydrothermal process, the magnesium silicate grew along the silica walls at the expense of consuming silica and deposited on the carbon surface of the C@SBA-15. Meanwhile, the rigid carbon inside the pores of the SBA-15 supported the magnesium silicate as mesoporous walls under hydrothermal condition. The obtained magnesium silicate possessed ordered mesoporous structure, high specific surface area of 446 m2/g, large pore volume of 0.84 cm3/g, and hierarchical structure assembled with ultrathin nanosheets of 15 nm in thickness. These characteristics endow the ordered mesoporous magnesium silicate with the fast adsorption rate and high adsorption capacity of 382 mg/g for methylene blue. In addition, this synthesis method opens a new approach to fabricate other ordered mesoporous silicates.

  20. Efficient synthesis and activity of beneficial intestinal flora of two lactulose-derived oligosaccharides.

    PubMed

    Zhu, Zhen-Yuan; Cui, Di; Gao, Hui; Dong, Feng-Ying; Liu, Xiao-cui; Liu, Fei; Chen, Lu; Zhang, Yong-min

    2016-05-23

    Lactulose is considered as a prebiotic because it promotes the intestinal proliferation of Lactobacillus acidophilus which is added to various milk products. Moreover, lactulose is used in pharmaceuticals as a gentle laxative and to treat hyperammonemia. This study was aimed at the total synthesis of two Lactulose-derived oligosaccharides: one is 3-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,3-glycosidic bound, the other is 1-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,1-glycosidic bound, which were accomplished in seven steps from d-fructose and β-d-galactose and every step of yield above 75%. This synthetic route provided a practical and effective synthetic strategy for galactooligosaccharides, starting from commercially available monosaccharides. Then we evaluated on their prebiotic properties in the search for potential agents of regulating and improving the intestinal flora of human. The result showed that the prebiotic properties of Lactulose-derived oligosaccharides was much better than Lactulose. Among them, 3-O-β-d-galactopyranosyl-d-fructose displayed the most potent activity of proliferation of L. acidophilus.

  1. Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives.

    PubMed

    Polo, Efrain; Trilleras, Jorge; Ramos, Juan; Galdámez, Antonio; Quiroga, Jairo; Gutierrez, Margarita

    2016-07-09

    A small series of tetrahydroindazoles was prepared, starting from 2-acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green method for the synthesis of substituted tetrahydroindazole derivatives. The in vitro antioxidant activity was evaluated using the DPPH and ABTS methods. In these assays, 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) showed moderate DPPH decoloring activity, while 3-methyl-4,5,6,7-tetrahydro-1H-indazole (3a), 3-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indazole (3b) and 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) were the most active in the ABTS assay. All compounds were well characterized by IR, ¹H-, (13)C-NMR and GC-MS spectroscopy and physical data, while the structure of 4-(3-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid (3e) was also determined by single crystal X-ray analysis.

  2. The Synthesis of Organic Molecules of Intrinsic Microporosity Designed to Frustrate Efficient Molecular Packing.

    PubMed

    Taylor, Rupert G D; Bezzu, C Grazia; Carta, Mariolino; Msayib, Kadhum J; Walker, Jonathan; Short, Rhys; Kariuki, Benson M; McKeown, Neil B

    2016-02-12

    Efficient reactions between fluorine-functionalised biphenyl and terphenyl derivatives with catechol-functionalised terminal groups provide a route to large, discrete organic molecules of intrinsic microporosity (OMIMs) that provide porous solids solely by their inefficient packing. By altering the size and substituent bulk of the terminal groups, a number of soluble compounds with apparent BET surface areas in excess of 600 m(2)  g(-1) are produced. The efficiency of OMIM structural units for generating microporosity is in the order: propellane>triptycene>hexaphenylbenzene>spirobifluorene>naphthyl=phenyl. The introduction of bulky hydrocarbon substituents significantly enhances microporosity by further reducing packing efficiency. These results are consistent with findings from previously reported packing simulation studies. The introduction of methyl groups at the bridgehead position of triptycene units reduces intrinsic microporosity. This is presumably due to their internal position within the OMIM structure so that they occupy space, but unlike peripheral substituents they do not contribute to the generation of free volume by inefficient packing.

  3. Easy synthesis approach of Pt-nanoparticles on polyaniline surface: an efficient electro-catalyst for methanol oxidation reaction

    NASA Astrophysics Data System (ADS)

    Mondal, Sanjoy; Malik, Sudip

    2016-10-01

    A facile room temperature and surfactant free synthesis of platinum nanoparticles (Pt-NPs) on benzene tetra-carboxylic acid doped polyaniline (BDP) tube has been successfully demonstrated by solution dipping method. Preparation of Pt-NPs has been done through a red-ox reaction between BDP tubes and Pt-salt, as BDP itself acts as nontoxic reducing agent as well as template cum stabilizer for Pt-NPs. In BDP@Pt composites, ∼2.5 ± 0.5 nm spherical shaped Pt-NPs as observed from TEM studies are nicely decorated on the surface of BDP. The population or the loading density of Pt-NPs on BDP tube is greatly controlled by changing the w/w ratio of BDP to H2PtCl6. Synthesized BDP@Pt composites are subsequently employed as an efficient electro-catalyst for methanol oxidation reaction (MOR) in acidic medium. Furthermore, the observed catalytic activity is consequently ∼12 times higher than that of commercially available Pt/C catalyst. Depending on the loading density of Pt-NPs on BDP tubes, the efficiency and carbon monoxide (CO) tolerance ability of composites have been explored.

  4. Shape-Controlled Synthesis of High-Quality Cu7 S4 Nanocrystals for Efficient Light-Induced Water Evaporation.

    PubMed

    Zhang, Changbo; Yan, Cong; Xue, Zhenjie; Yu, Wei; Xie, Yinde; Wang, Tie

    2016-10-01

    Copper sulfides (Cu2-x S), are a novel kind of photothermal material exhibiting significant photothermal conversion efficiency, making them very attractive in various energy conversion related devices. Preparing high quality uniform Cu2-x S nanocrystals (NCs) is a top priority for further energy-and sustainability relevant nanodevices. Here, a shape-controlled high quality Cu7 S4 NCs synthesis strategy is reported using sulfur in 1-octadecene as precursor by varying the heating temperature, as well as its forming mechanism. The performance of the Cu7 S4 NCs is further explored for light-driven water evaporation without the need of heating the bulk liquid to the boiling point, and the results suggest that as-synthesized highly monodisperse NCs perform higher evaporation rate than polydisperse NCs under the identical morphology. Furthermore, disk-like NCs exhibit higher water evaporation rate than spherical NCs. The water evaporation rate can be further enhanced by assembling the organic phase Cu7 S4 NCs into a dense film on the aqueous solution surface. The maximum photothermal conversion efficiency is as high as 77.1%.

  5. Gene cloning and molecular characterization of the Talaromyces thermophilus lipase catalyzed efficient hydrolysis and synthesis of esters.

    PubMed

    Romdhane, Ines Belhaj-Ben; Frikha, Fakher; Maalej-Achouri, Inès; Gargouri, Ali; Belghith, Hafedh

    2012-02-15

    A genomic bank from Talaromyces thermophilus fungus was constructed and screened using a previously isolated fragment lipase gene as probe. From several clones isolated, the nucleotide sequence of the lipase gene (TTL gene) was completed and sequenced. The TTL coding gene consists of an open reading frame (ORF) of 1083bp encoding a protein of 269 Aa with an estimated molecular mass of 30kDa. The TTL belongs to the same gene family as Thermomyces lanuginosus lipase (TLL, Lipolase®), a well known lipase with multiple applications. The promoter sequence of the TTL gene showed the conservation of known consensus sequences PacC, CreA, Hap2-3-4 and the existence of a particular sequence like the binding sites of Oleate Response Element (ORE) and Fatty acids Responsis Element (FARE) which are similar to that already found to be specific of lipolytic genes in Candida and Fusarium, respectively. Northern blot analysis showed that the TTL expression was much higher on wheat bran than on olive oil as sole carbon source. Compared to the Lipolase®, this enzyme was found to be more efficient for the hydrolysis and the synthesis of esters; and its synthetic efficiency even reached 91.6% from Waste Cooking Oil triglycerides.

  6. Efficient Lewis acid ionic liquid-catalyzed synthesis of the key intermediate of coenzyme Q10 under microwave irradiation.

    PubMed

    Chen, Yue; Zu, Yuangang; Fu, Yujie; Zhang, Xuan; Yu, Ping; Sun, Guoyong; Efferth, Thomas

    2010-12-22

    An efficient synthesis of a valuable intermediate of coenzyme Q(10) by microwave-assisted Lewis acidic ionic liquid (IL)-catalyzed Friedel-Crafts alkylation is reported. The acidity of six [Etpy]BF(4)-based ionic liquids was characterized by means of the FT-IR technique using acetonitrile as a molecular probe. The catalytic activities of these ionic liquids were correlated with their Lewis acidity. With increasing Lewis acid strength of the ionic liquids, their catalytic activity in the Friedel-Crafts reaction increased, except for [Etpy]BF(4)-AlCl(3). The effects of the reaction system, the molar fraction of Lewis acid in the Lewis acid ILs and heating techniques were also investigated. Among the six Lewis acid ionic liquids tested [Etpy]BF(4)-ZnCl(2) showed the best catalytic activity, with a yield of 89% after a very short reaction time (150 seconds). This procedure has the advantages of higher efficiency, better reusability of ILs, energy conservation and eco-friendliness. The method has practical value for preparation of CoQ(10) on an industrial scale.

  7. Synthesis of Bismuth-Nanoparticle-Enriched Nanoporous Carbon on Graphene for Efficient Electrochemical Analysis of Heavy-Metal Ions.

    PubMed

    Cui, Lin; Wu, Jie; Ju, Huangxian

    2015-08-03

    A BiNPs@NPCGS nanocomposite was designed for highly efficient detection of multiple heavy-metal ions by in situ synthesis of bismuth-nanoparticle (BiNP)-enriched nanoporous carbon (NPS) on graphene sheet (GS). The NPCGS was prepared by pyrolysis of zeolitic imidazolate framework-8 (ZIF-8) nanocrystals deposited on graphene oxide and displayed a high surface area of 1251 m(2)  g(-1) and a pore size of 3.4 nm. BiNPs were deposited on NPCGS in situ by chemical reduction of Bi(3+) with NaBH4 . Due to the restrictive effect of the pore/surface structure of NPCGS, the BiNPs were uniform and well dispersed on the NPCGS. The BiNPs@NPCGS showed good conductivity and high effective area, and the presence of BiNPs allowed it to act as an efficient material for anodic-stripping voltammetric detection of heavy-metal ions. Under optimized conditions, the BiNPs@NPCGS-based sensor could simultaneously determine Pb(2+) and Cd(2+) with detection limits of 3.2 and 4.1 nM, respectively. Moreover, the proposed sensor could also differentiate Tl(+) from Pb(2+) and Cd(2+). Owing to its advantages of simple preparation, environmental friendliness, high surface area, and fast electron-transfer ability, BiNPs@NPCGS showed promise for practical application in sensing heavy-metal ions.

  8. Green synthesis of highly efficient CdSe quantum dots for quantum-dots-sensitized solar cells

    SciTech Connect

    Gao, Bing; Shen, Chao; Zhang, Mengya; Yuan, Shuanglong; Yang, Yunxia E-mail: grchen@ecust.edu.cn; Chen, Guorong E-mail: grchen@ecust.edu.cn; Zhang, Bo

    2014-05-21

    Green synthesis of CdSe quantum dots for application in the quantum-dots-sensitized solar cells (QDSCs) is investigated in this work. The CdSe QDs were prepared with glycerol as the solvent, with sharp emission peak, full width at half maximum around 30 nm, and absorption peak from 475 nm to 510 nm. The reaction is environmental friendly and energy saving. What's more, the green synthesized CdSe QDs are coherence to the maximum remittance region of the solar spectrum and suitable as sensitizers to assemble onto TiO{sub 2} electrodes for cell devices application. What's more, the dynamic procedure of the carriers' excitation, transportation, and recombination in the QDSCs are discussed. Because the recombination of the electrons from the conduction band of TiO{sub 2}'s to the electrolyte affects the efficiency of the solar cells greatly, 3-Mercaptopropionic acid capped water-dispersible QDs were used to cover the surface of TiO{sub 2}. The resulting green synthesized CdSe QDSCs with Cu{sub 2}S as the electrode show a photovoltaic performance with a conversion efficiency of 3.39%.

  9. Controllable synthesis of α-sulfur spheres with hierarchical nanostructures for efficient visible-light-driven photocatalytic ability

    NASA Astrophysics Data System (ADS)

    Dang, Xueming; Zhang, Xiufang; Zhang, Weiqiang; Dong, Xiaoli; Wang, Guowen; Ma, Hongchao

    2015-08-01

    Visible-light-active α-sulfur spheres with hierarchical nanostructures were fabricated by simple solution-phase synthesis with PVP as the template for enhanced photocatalytic ability. The α-sulfur hierarchical spheres with an ultrahigh specific surface area can controllable synthesized by changing the addition quantity of PVP. The obtained products are systematically studied by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-vis absorption spectroscopy (DRS), Fluorescence (FL) and Brunauer-Emmett-Teller (BET). The photocatalytic activity of the as-prepared samples is evaluated by photocatalytic degradation of Rhodamine B (RhB) aqueous solution under visible light illumination. The results indicate that the morphology, specific surface area, photo absorbance ability, the separation efficiency of photogenerated carriers and the reactant adsorption performance can be controlled by varying the addition quantity of PVP. When 200 mg PVP is added, α-sulfur hierarchical spheres with uniform particle size about 1 μm and ultrahigh specific surface area of 67.1 m2/g is obtained, and its photocatalytic activity reaches a maximum value, which can be attributed to the combined effects of photo absorbance ability, the separation efficiency of photogenerated carriers and the reactant adsorption performance.

  10. [1+1+1] Cyclotrimerization for the Synthesis of Cyclopropanes

    PubMed Central

    Manna, Srimanta

    2016-01-01

    Abstract The synthesis of small rings by functionalization of C(sp3)−H bonds remains a great challenge. We report for the first time a copper‐catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone. The developed transformation is based on an extraordinary copper‐catalyzed cascade process that allows saturated carbocycles to be obtained for the first time by cyclotrimerization through functionalization of C(sp3)−H bonds. The cascade of sixfold C(sp3)−H bond functionalization allows the synthesis of cyclopropanes in a highly stereoselective approach. PMID:26997466

  11. Functionalization of mesoporous carbon with superbasic MgO nanoparticles for the efficient synthesis of sulfinamides.

    PubMed

    Chakravarti, Rajashree; Mano, Ajayan; Iwai, Hideo; Aldeyab, Salem S; Kumar, R Pradeep; Kantam, M Lakshmi; Vinu, Ajayan

    2011-06-06

    Highly basic MgO nanoparticles with different sizes have been successfully immobilized over mesoporous carbon with different pore diameters by a simple wet-impregnation method. The prepared catalysts have been characterized by various sophisticated techniques, such as XRD, nitrogen adsorption, electron energy loss spectroscopy, high-resolution TEM, X-ray photoelectron spectroscopy, and the temperature-programmed desorption of CO(2). XRD results reveal that the mesostructure of the support is retained even after the huge loading of MgO nanoparticles inside the mesochannels of the support. It is also demonstrated that the particle size and dispersion of the MgO nanoparticles on the support can be finely controlled by the simple adjustment of the textural parameters of the supports. Among the support materials studied, mesoporous carbon with the largest pore diameter and large pore volume offered highly crystalline small-size cubic-phase MgO nanoparticles with a high dispersion. The basicity of the MgO-supported mesoporous carbons can also be controlled by simply changing the loading of the MgO and the pore diameter of the support. These materials have been employed as heterogeneous catalysts for the first time in the selective synthesis of sulfinamides. Among the catalysts investigated, the support with the large pore diameter and high loading of MgO showed the highest activity with an excellent yield of sulfinamides. The catalyst also showed much higher activity than the pristine MgO nanoparticles. The effects of the reaction parameters, including the solvents and reaction temperature, and textural parameters of the supports in the activity of the catalyst have also been demonstrated. Most importantly, the catalyst was found to be highly stable, showing excellent activity even after the third cycle of reaction.

  12. Simple synthesis of cobalt sulfide nanorods for efficient electrocatalytic oxidation of vanillin in food samples.

    PubMed

    Sivakumar, Mani; Sakthivel, Mani; Chen, Shen-Ming

    2017-03-15

    Well-defined CoS nanorods (NR) were synthesized using a simple hydrothermal method, and were tested as an electrode material for electro-oxidation of vanillin. The NR material was characterized with regard to morphology, crystallinity, and electro-activity by use of appropriate analytical techniques. The resulting CoS NR@Nafion modified glassy carbon electrode (GCE) exhibited efficient electro-oxidation of vanillin with a considerable linear range of current-vs-concentration (0.5-56μM vanillin) and a detection limit of 0.07μM. Also, food samples containing vanillin were studied to test suitability for commercial applications.

  13. Simple, Efficient and Controllable Synthesis of Iodo/Di-iodoarenes via Ipsoiododecarboxylation/Consecutive Iodination Strategy

    NASA Astrophysics Data System (ADS)

    Yang, Yun; Zhang, Lijuan; Deng, Guo-Jun; Gong, Hang

    2017-01-01

    A practical, efficient, and operationally simple strategy for the ipsoiododecarboxylation and di-iodination of aromatic carboxylic acids using the low-cost commercial reagent succinimide (NIS) as iodine source is reported. This iodination or di-iodination process can be easily controlled through reaction conditions, thereby providing corresponding iodination or di-iodination products with high yields. Furthermore, these two reactions can be easily scaled up to gram-scale by using palladium catalyst (0.66 mol%), which provides high isolated yield.

  14. Simple, Efficient and Controllable Synthesis of Iodo/Di-iodoarenes via Ipsoiododecarboxylation/Consecutive Iodination Strategy

    PubMed Central

    Yang, Yun; Zhang, Lijuan; Deng, Guo-Jun; Gong, Hang

    2017-01-01

    A practical, efficient, and operationally simple strategy for the ipsoiododecarboxylation and di-iodination of aromatic carboxylic acids using the low-cost commercial reagent succinimide (NIS) as iodine source is reported. This iodination or di-iodination process can be easily controlled through reaction conditions, thereby providing corresponding iodination or di-iodination products with high yields. Furthermore, these two reactions can be easily scaled up to gram-scale by using palladium catalyst (0.66 mol%), which provides high isolated yield. PMID:28091536

  15. Design and synthesis of molecular donors for solution-processed high-efficiency organic solar cells.

    PubMed

    Coughlin, Jessica E; Henson, Zachary B; Welch, Gregory C; Bazan, Guillermo C

    2014-01-21

    Organic semiconductors incorporated into solar cells using a bulk heterojunction (BHJ) construction show promise as a cleaner answer to increasing energy needs throughout the world. Organic solar cells based on the BHJ architecture have steadily increased in their device performance over the past two decades, with power conversion efficiencies reaching 10%. Much of this success has come with conjugated polymer/fullerene combinations, where optimized polymer design strategies, synthetic protocols, device fabrication procedures, and characterization methods have provided significant advancements in the technology. More recently, chemists have been paying particular attention to well-defined molecular donor systems due to their ease of functionalization, amenability to standard organic purification and characterization methods, and reduced batch-to-batch variability compared to polymer counterparts. There are several critical properties for efficient small molecule donors. First, broad optical absorption needs to extend towards the near-IR region to achieve spectral overlap with the solar spectrum. Second, the low lying highest occupied molecular orbital (HOMO) energy levels need to be between -5.2 and -5.5 eV to ensure acceptable device open circuit voltages. Third, the structures need to be relatively planar to ensure close intermolecular contacts and high charge carrier mobilities. And last, the small molecule donors need to be sufficiently soluble in organic solvents (≥10 mg/mL) to facilitate solution deposition of thin films of appropriate uniformity and thickness. Ideally, these molecules should be constructed from cost-effective, sustainable building blocks using established, high yielding reactions in as few steps as possible. The structures should also be easy to functionalize to maximize tunability for desired properties. In this Account, we present a chronological description of our thought process and design strategies used in the development of highly

  16. Efficient synthesis and reaction kinetics of readily water soluble esters containing sulfonic groups.

    PubMed

    Idzik, Krzysztof R; Nödler, Karsten; Maier, Friedrich; Licha, Tobias

    2014-12-15

    A series of various readily water soluble esters were synthesized by a very efficient procedure. These compounds can be useful as thermosensitive tracers for studying the cooling progress in a low enthalpy georeservoir exploitable by double flash geothermal power plant systems. The kinetics of their hydrolysis was investigated. Acylation of primary alcohols or phenols was carried out by a method based on a single-phase solvent system consisting of ethyl acetate acting as an organic solvent and triethylamine acting as a catalyst. Products were characterized by 1H-NMR, and 13C-NMR.

  17. An efficient algorithm for antenna synthesis updating following null-constraint changes

    NASA Astrophysics Data System (ADS)

    Magdy, M. A.; Paoloni, F. J.; Cheah, J. Y. C.

    1985-08-01

    The procedure to maximize the array signal to noise ratio with null constraints involves an optimization problem that can be solved efficiently using a modified Cholesky decomposition (UD) technique. Following changes in the main lobe and/or null positions, the optimal element weight vector can be updated without the need for a new complete matrix inversion. Some properties of the UD technique can be utilized such that the updating algorithm reprocesses only a part of the unit triangular matrix U. Proper ordering of matrix entries can minimize the dimension of the updated part.

  18. A High Performance Platform Based on cDNA Display for Efficient Synthesis of Protein Fusions and Accelerated Directed Evolution.

    PubMed

    Naimuddin, Mohammed; Kubo, Tai

    2016-02-08

    We describe a high performance platform based on cDNA display technology by developing a new modified puromycin linker-oligonucleotide. The linker consists of four major characteristics: a "ligation site" for hybridization and ligation of mRNA by T4 RNA ligase, a "puromycin arm" for covalent linkage of the protein, a "polyadenosine site" for a longer puromycin arm and purification of protein fusions (optional) using oligo-dT matrices, and a "reverse transcription site" for the formation of stable cDNA protein fusions whose cDNA is covalently linked to its encoded protein. The linker was synthesized by a novel branching strategy and provided >8-fold higher yield than previous linkers. This linker enables rapid and highly efficient ligation of mRNA (>90%) and synthesis of protein fusions (∼ 50-95%) in various cell-free expression systems. Overall, this new cDNA display method provides 10-200 fold higher end-usage fusions than previous methods and benefits higher diversity libraries crucial for directed protein/peptide evolution. With the increased efficiency, this system was able to reduce the time for one selection cycle to <8 h and is potentially amenable to high-throughput systems. We demonstrate the efficiency of this system for higher throughput selections of various biomolecular interactions and achieved 30-40-fold enrichment per selection cycle. Furthermore, a 4-fold higher enrichment of Flag-tag was obtained from a doped mixture compared with that of the previous cDNA display method. A three-finger protein library was evolved to isolate superior nanomolar range binding candidates for vascular endothelial growth factor. This method is expected to provide a beneficial impact to accelerated drug discovery and proteome analysis.

  19. Total synthesis of (±)-epithuriferic acid methyl ester via Diels-Alder reaction.

    PubMed

    Koprowski, Marek; Bałczewski, Piotr; Owsianik, Krzysztof; Różycka-Sokołowska, Ewa; Marciniak, Bernard

    2016-02-07

    In this paper, we have described the first total synthesis of (±)-epithuriferic acid methyl ester from non-natural sources, in four steps (20% overall yield). The key step involves the Diels-Alder reaction of isobenzofuran with methyl 3-(dimethoxyphosphoryl)acrylate which is controlled by "ortho" regio- and endo stereoselectivities due to the COOMe group.

  20. Synthesis and trimethylaluminum additions on gamma-hydroxy-delta-sulfinyl and sulfonyl enoates.

    PubMed

    Carreño, M Carmen; Sanz-Cuesta, M Jesús; Colobert, Françoise; Solladié, Guy

    2004-09-30

    [reaction: see text] The stereoselective synthesis of epimeric (R)- and (S)-gamma-hydroxy-delta-p-tolylsulfinyl (or sulfonyl) enoates is reported. Reaction with AlMe3 occurred exclusively at the ester group allowing a clean and high-yielding access to enantiopure 1,4-diols bearing a tertiary carbinol.

  1. 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…

  2. Asymmetric synthesis of Crispine A: constructing tetrahydroisoquinoline scaffolds using pummerer cyclizations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For the first time, a concise, linear and protecting group-free stereoselective synthesis of both enantiomers of crispine A have been achieved in six steps with an overall yield of less than or equal to 20%,starting from commercially available veratraldehyde. Asymmetric Keck allylation and trifluoro...

  3. Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature

    NASA Astrophysics Data System (ADS)

    Si, Weili; Zhang, Xuan; Lu, Shirong; Yasuda, Takeshi; Asao, Naoki; Han, Liyuan; Yamamoto, Yoshinori; Jin, Tienan

    2015-09-01

    Discovery of an efficient, practical, and flexible synthetic method to produce various important electron acceptors for low-cost organic photovoltaics (OPVs) is highly desirable. Although the most commonly used acceptor materials, such as PC61BM, PC71BM, IC60BA, bisPC61BM have been proved to be promising for the OPVs, they are still very expensive mainly due to their low production yields and limited synthetic methods. Herein, we report an unprecedented and innovative synthetic method of a variety of fullerene mono- and biscycloadducts by using manganese powder as a promotor. The reaction of fullerenes with various dibromides proceeds efficiently and selectively under very mild conditions to give the corresponding cycloadducts in good to excellent yields. The combination of manganese power with DMSO additive is crucial for the successful implementation of the present cycloaddition. Notably, the standard OPV acceptors, such as PCBMs, have been obtained in extraordinarily high yields, which cannot be achieved under the previously reported methods.

  4. Efficient synthesis of poly(2-vinylpyridine)-silica colloidal nanocomposite particles using a cationic azo initiator.

    PubMed

    Dupin, Damien; Schmid, Andreas; Balmer, Jennifer A; Armes, Steven P

    2007-11-06

    Colloidal poly(2-vinylpyridine)-silica nanocomposite particles can be efficiently prepared by emulsion polymerization at 60 degrees C using a commercial 20 nm aqueous silica sol as the sole stabilizing agent. Unlike previously reported colloidal nanocomposite syntheses, transmission electron microscopy studies indicate very high silica aggregation efficiencies (88-99%). The key to success is simply the selection of a suitable cationic azo initiator. In contrast, the use of an anionic persulfate initiator leads to substantial contamination of the nanocomposite particles with excess silica sol. The cationic azo initiator is electrostatically adsorbed onto the anionic silica sol at submonolayer coverage, which suggests that surface polymerization may be important for successful nanocomposite formation. Moreover, the 2-vinylpyridine can be partially replaced with either styrene or methacrylic comonomers to produce a range of copolymer-silica nanocomposite particles. The poly(2-vinylpyridine)-silica nanocomposite particles have a well-defined core-shell morphology, with poly(2-vinylpyridine) cores and silica shells; mean diameters typically vary from 180 to 220 nm, and mean silica contents range from 27 to 35% by mass.

  5. Synthesis and characterization of VO2-based thermochromic thin films for energy-efficient windows

    NASA Astrophysics Data System (ADS)

    Batista, Carlos; Ribeiro, Ricardo M.; Teixeira, Vasco

    2011-12-01

    Thermochromic VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC and pulsed-DC magnetron sputtering. The influence of substitutional doping of V by higher valence cations, such as W, Mo, and Nb, and respective contents on the crystal structure of VO2 is evaluated. Moreover, the effectiveness of each dopant element on the reduction of the intrinsic transition temperature and infrared modulation efficiency of VO2 is discussed. In summary, all the dopant elements--regardless of the concentration, within the studied range-- formed a solid solution with VO2, which was the only compound observed by X-ray diffractometry. Nb showed a clear detrimental effect on the crystal structure of VO2. The undoped films presented a marked thermochromic behavior, specially the one prepared by pulsed-DC sputtering. The dopants effectively decreased the transition of VO2 to the proximity of room temperature. However, the IR modulation efficiency is markedly affected as a consequence of the increased metallic character of the semiconducting phase. Tungsten proved to be the most effective element on the reduction of the semiconducting-metal transition temperature, while Mo and Nb showed similar results with the latter being detrimental to the thermochromism.

  6. Synthesis and characterization of VO2-based thermochromic thin films for energy-efficient windows.

    PubMed

    Batista, Carlos; Ribeiro, Ricardo M; Teixeira, Vasco

    2011-04-07

    Thermochromic VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC and pulsed-DC magnetron sputtering. The influence of substitutional doping of V by higher valence cations, such as W, Mo, and Nb, and respective contents on the crystal structure of VO2 is evaluated. Moreover, the effectiveness of each dopant element on the reduction of the intrinsic transition temperature and infrared modulation efficiency of VO2 is discussed. In summary, all the dopant elements--regardless of the concentration, within the studied range-- formed a solid solution with VO2, which was the only compound observed by X-ray diffractometry. Nb showed a clear detrimental effect on the crystal structure of VO2. The undoped films presented a marked thermochromic behavior, specially the one prepared by pulsed-DC sputtering. The dopants effectively decreased the transition of VO2 to the proximity of room temperature. However, the IR modulation efficiency is markedly affected as a consequence of the increased metallic character of the semiconducting phase. Tungsten proved to be the most effective element on the reduction of the semiconducting-metal transition temperature, while Mo and Nb showed similar results with the latter being detrimental to the thermochromism.

  7. Hydroxamic Acids in Asymmetric Synthesis

    PubMed Central

    Li, Zhi; Yamamoto, Hisashi

    2012-01-01

    Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst’s center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed. Due to their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless Asymmetric Epoxidation, which uses titanium-tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydroxamic acid as catalysts since then. This Account summarizes our research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as chiral ligands. We designed and synthesized a series of new hydroxamic acids, most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed epoxidation of allylic and homoallylic alcohols achieved higher activity and stereoselectivity than Sharpless Asymmetric Epoxidation in many cases. Changing the metal species led to a series of unprecedented asymmetric epoxidation reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely functionalized chiral epoxides with good yields and enantioselectivities. PMID:23157425

  8. Common Distribution of gad Operon in Lactobacillus brevis and its GadA Contributes to Efficient GABA Synthesis toward Cytosolic Near-Neutral pH

    PubMed Central

    Wu, Qinglong; Tun, Hein Min; Law, Yee-Song; Khafipour, Ehsan; Shah, Nagendra P.

    2017-01-01

    Many strains of lactic acid bacteria (LAB) and bifidobacteria have exhibited strain-specific capacity to produce γ-aminobutyric acid (GABA) via their glutamic acid decarboxylase (GAD) system, which is one of amino acid-dependent acid resistance (AR) systems in bacteria. However, the linkage between bacterial AR and GABA production capacity has not been well established. Meanwhile, limited evidence has been provided to the global diversity of GABA-producing LAB and bifidobacteria, and their mechanisms of efficient GABA synthesis. In this study, genomic survey identified common distribution of gad operon-encoded GAD system in Lactobacillus brevis for its GABA production among varying species of LAB and bifidobacteria. Importantly, among four commonly distributed amino acid-dependent AR systems in Lb. brevis, its GAD system was a major contributor to maintain cytosolic pH homeostasis by consuming protons via GABA synthesis. This highlights that Lb. brevis applies GAD system as the main strategy against extracellular and intracellular acidification demonstrating its high capacity of GABA production. In addition, the abundant GadA retained its activity toward near-neutral pH (pH 5.5–6.5) of cytosolic acidity thus contributing to efficient GABA synthesis in Lb. brevis. This is the first global report illustrating species-specific characteristic and mechanism of efficient GABA synthesis in Lb. brevis. PMID:28261168

  9. Common Distribution of gad Operon in Lactobacillus brevis and its GadA Contributes to Efficient GABA Synthesis toward Cytosolic Near-Neutral pH.

    PubMed

    Wu, Qinglong; Tun, Hein Min; Law, Yee-Song; Khafipour, Ehsan; Shah, Nagendra P

    2017-01-01

    Many strains of lactic acid bacteria (LAB) and bifidobacteria have exhibited strain-specific capacity to produce γ-aminobutyric acid (GABA) via their glutamic acid decarboxylase (GAD) system, which is one of amino acid-dependent acid resistance (AR) systems in bacteria. However, the linkage between bacterial AR and GABA production capacity has not been well established. Meanwhile, limited evidence has been provided to the global diversity of GABA-producing LAB and bifidobacteria, and their mechanisms of efficient GABA synthesis. In this study, genomic survey identified common distribution of gad operon-encoded GAD system in Lactobacillus brevis for its GABA production among varying species of LAB and bifidobacteria. Importantly, among four commonly distributed amino acid-dependent AR systems in Lb. brevis, its GAD system was a major contributor to maintain cytosolic pH homeostasis by consuming protons via GABA synthesis. This highlights that Lb. brevis applies GAD system as the main strategy against extracellular and intracellular acidification demonstrating its high capacity of GABA production. In addition, the abundant GadA retained its activity toward near-neutral pH (pH 5.5-6.5) of cytosolic acidity thus contributing to efficient GABA synthesis in Lb. brevis. This is the first global report illustrating species-specific characteristic and mechanism of efficient GABA synthesis in Lb. brevis.

  10. A facile synthesis of highly stable modified carbon nanotubes as efficient oxygen reduction reaction catalysts

    NASA Astrophysics Data System (ADS)

    Stenmark, Theodore Axel

    Proton Exchange Membrane Fuel Cell (PEMFC) technology is an exciting alternative energy prospect, especially in the field of transportation. PEMFCs are three times as efficient as internal combustion (IC) engines and emit only water as a byproduct. The latter point is especially important in a day and age when climate change is upon us. However, platinum required to catalyze the sluggish oxygen reduction reaction (ORR) which takes place on the cathode of the PEMFC has rendered fuel cell automobiles economically unviable. Therefore, the pursuit of an inexpensive replacement for platinum has become an active research area. Herein, a facile synthetic process for modified carbon nanotubes for ORR catalysis is described. These nanotubes display catalytic activity via rotating disc electrode (RDE) analysis which, in some cases, equals that of a Pt/C standard.

  11. Renewable rigid diamines: efficient, stereospecific synthesis of high purity isohexide diamines.

    PubMed

    Thiyagarajan, Shanmugam; Gootjes, Linda; Vogelzang, Willem; van Haveren, Jacco; Lutz, Martin; van Es, Daan S

    2011-12-16

    We report an efficient three-step strategy for synthesizing rigid, chiral isohexide diamines derived from 1,4:3,6-dianhydrohexitols. These biobased chiral building blocks are presently the subject of several investigations (in our and several other groups) because of their application in high-performance biobased polymers, such as polyamides and polyurethanes. Among the three possible stereo-isomers, dideoxy-diamino isoidide and dideoxy-diamino isosorbide can be synthesized from isomannide and isosorbide respectively in high yield with absolute stereo control. Furthermore, by using this methodology dideoxy-amino isomannide-a tricyclic adduct-was obtained starting from isoidide in high yield. Our improved synthetic route is a valuable advance towards meeting scale and purity demands for evaluating the properties of new biobased performance materials, which will benefit the development of these plastics.

  12. Rational Design and Synthesis of Efficient Sunscreens To Boost the Solar Protection Factor.

    PubMed

    Losantos, Raúl; Funes-Ardoiz, Ignacio; Aguilera, José; Herrera-Ceballos, Enrique; García-Iriepa, Cristina; Campos, Pedro J; Sampedro, Diego

    2017-03-01

    Skin cancer incidence has been increasing in the last decades, but most of the commercial formulations used as sunscreens are designed to protect only against solar erythema. Many of the active components present in sunscreens show critical weaknesses, such as low stability and toxicity. Thus, the development of more efficient components is an urgent health necessity and an attractive industrial target. We have rationally designed core moieties with increased photoprotective capacities and a new energy dissipation mechanism. Using these scaffolds, we have synthesized a series of compounds with tunable properties suitable for their use in sunscreens, and enhanced properties in terms of stability, light energy dissipation, and toxicity. Moreover, some representative compounds were included in final sunscreen formulations and a relevant solar protection factor boost was measured.

  13. Practical and Efficient Synthesis of α-Aminophosphonic Acids Containing 1,2,3,4-Tetrahydroquinoline or 1,2,3,4-Tetrahydroisoquinoline Heterocycles.

    PubMed

    Ordóñez, Mario; Arizpe, Alicia; Sayago, Fracisco J; Jiménez, Ana I; Cativiela, Carlos

    2016-08-31

    We report here a practical and efficient synthesis of α-aminophosphonic acid incorporated into 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline heterocycles, which could be considered to be conformationally constrained analogues of pipecolic acid. The principal contribution of this synthesis is the introduction of the phosphonate group in the N-acyliminium ion intermediates, obtained from activation of the quinoline and isoquinoline heterocycles or from the appropriate δ-lactam with benzyl chloroformate. Finally, the hydrolysis of phosphonate moiety with simultaneous cleavage of the carbamate afforded the target compounds.

  14. Efficient Synthesis of β-Aryl-γ-lactams and Their Resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen.

    PubMed

    Montoya-Balbás, Iris J; Valentín-Guevara, Berenice; López-Mendoza, Estefanía; Linzaga-Elizalde, Irma; Ordoñez, Mario; Román-Bravo, Perla

    2015-12-10

    An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride.

  15. Concise Total Synthesis of Trichodermamides A, B and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core

    PubMed Central

    Mfuh, Adelphe M.; Zhang, Yu; Stephens, David E.; Vo, Anh X. T.; Arman, Hadi D.; Larionov, Oleg V.

    2016-01-01

    We report herein a facile and efficient method of the construction of the cis-1,2-oxazadecaline system, distinctive of (pre)trichodermamides, aspergillazine A, gliovirin and FA-2097. The formation of the 1,2-oxazadecaline core was accomplished by a 1,2-addition of an αC-lithiated O-silyl ethyl pyruvate oxime to benzoquinone, that is followed by an oxa-Michael ring-closure. The method was successfully applied to the concise total synthesis of trichodermamide A (in gram quantities), trichodermamide B, as well as the first synthesis of trichodermamide C. PMID:26084356

  16. Stacking and Electrostatic Interactions Drive the Stereoselectivity of Silylium-Ion Asymmetric Counteranion-Directed Catalysis.

    PubMed

    Seguin, Trevor J; Wheeler, Steven E

    2016-12-19

    Computational analysis shows that the enantioselectivity of asymmetric Lewis-acid organocatalysis of the Diels-Alder cycloaddition of cyclopentadiene to cinnamates arises from stacking interactions that favor the addition of the diene to the more hindered face of the dienophile, while electrostatic interactions control the diastereoselectivity by selectively stabilizing the endo transition state. These results not only explain the stereoselectivity of these silylium-ion-ACDC reactions but should also guide the development of more effective ion-pairing asymmetric organocatalysts.

  17. Nickel-Catalyzed Stereoselective Alkenylation of C(sp(3))-H Bonds with Terminal Alkynes.

    PubMed

    Lin, Cong; Chen, Zhengkai; Liu, Zhanxiang; Zhang, Yuhong

    2017-02-17

    A nickel-catalyzed stereoselective alkenylation of an unactivated β-C(sp(3))-H bond in aliphatic amide with terminal alkynes using 8-aminoquinoline auxiliary is reported for the first time. This reaction displays excellent functional group tolerance with respect to both aliphatic amides and terminal alkynes and features a cheap nickel catalytic system. The 8-aminoquinolyl directing group could be smoothly removed, and the resultant β-styrylcarboxylic acid derivatives could serve as versatile building blocks for further transformation.

  18. Enhancement of toxicity and enzyme-repressing activity of p-dioxane by chlorination: stereoselective effects.

    PubMed

    Woo, Y T; Neuburger, B J; Arcos, J C; Argus, M F; Nishiyama, K; Griffin, G W

    1980-01-01

    The acute toxicity of p-dioxane may be enhanced up to 1000-fold by chlorination of the compound. The effect was stereoselective. Of the stereoisomers tested, tetrachloro-p-dioxane, isomer I (2r, 3t, 5t, 6c) was over 80 times more toxic than isomer II (2r, 3c, 5t, 6t). The latter compound was also a potent repressor of hepatic dimethylnitrosamine-demethylase I (DMN-d) and aryl hydrocarbon hydroxylase (AHH).

  19. Intramolecular Diels–Alder Reactions of Cycloalkenones: Stereoselectivity, Lewis Acid Acceleration, and Halogen Substituent Effects

    PubMed Central

    2015-01-01

    The intramolecular Diels–Alder reactions of cycloalkenones and terminal dienes occur with high endo stereoselectivity, both thermally and under Lewis-acidic conditions. Through computations, we show that steric repulsion and tether conformation govern the selectivity of the reaction, and incorporation of either BF3 or α-halogenation increases the rate of cycloaddition. With a longer tether, isomerization from a terminal diene to the more stable internal diene results in a more facile cycloaddition. PMID:24410341

  20. Structural Determinants for the Stereoselective Hydrolysis of Chiral Substrates by Phosphotriesterase

    SciTech Connect

    Tsai, P.; Fan, Y; Kim, J; Yang, L; Almo, S; Gao, Y; Raushel, F

    2010-01-01

    Wild-type phosphotriesterase (PTE) preferentially hydrolyzes the R{sub P} enantiomers of the nerve agents sarin (GB) and cyclosarin (GF) and their chromophoric analogues. The active site of PTE can be subdivided into three binding pockets that have been denoted as the small, large, and leaving group pockets based on high-resolution crystal structures. The sizes and shapes of these pockets dictate the substrate specificity and stereoselectivity for catalysis. Mutants of PTE that exhibit substantial changes in substrate specificity and the ability to differentiate between chiral substrates have been prepared. For example, the G60A mutant is stereoselective for the hydrolysis of the R{sub P} enantiomer of the chromophoric analogues of sarin and cyclosarin, whereas the H254G/H257W/L303T (GWT) mutant reverses the stereoselectivity for the enantiomers of these two compounds. Molecular dynamics simulations and high-resolution X-ray structures identified the correlations between structural changes in the active site and the experimentally determined kinetic parameters for substrate hydrolysis. New high-resolution structures were determined for the H257Y/L303T (YT), I106G/F132G/H257Y (GGY), and H254Q/H257F (QF) mutants of PTE. Molecular dynamics calculations were conducted using the SP and RP enantiomers of the analogues for sarin and cyclosarin for the wild-type PTE and the G60A, YT, GGY, QF, and GWT mutants. The experimental stereoselectivity correlated nicely with the difference in the computed angle of attack for the nucleophilic hydroxide relative to the phenolic leaving group of the substrate.

  1. Stereoselective sulfate conjugation of racemic 4-hydroxypropranolol by human and rat liver cytosol

    SciTech Connect

    Walle, T.; Walle, U.K. )

    1991-03-01

    The objective of this study was to determine the stereochemistry of sulfoconjugation of a chiral phenolic amine drug, 4-hydroxypropranolol (HOP), by the human liver. The reaction was catalyzed by the 100,000 g cytosol as the phenolsulfotransferase (PST) enzyme source with PAP35S as the co-substrate. The enantiomers of the intact sulfate conjugate formed, (+)-HOP35S and (-)-HOP35S, were separated by HPLC and measured by liquid scintillation spectrometry. Complex velocity vs. substrate concentration curves were obtained with two peaks of activity, one at 3 microM (high affinity) and one at 500 microM (low affinity). The high-affinity reaction demonstrated a high degree of stereoselectivity. Whereas the affinity of the enantiomers for this reaction was identical, with a very low apparent KM value of 0.59 microM, the apparent Vmax value for (+)-HOPS formation was 4.6-fold higher than for (-)-HOPS. In sharp contrast, the low-affinity reaction, with an apparent KM of 65 microM, was not stereoselective. Inhibition of the high-affinity reaction by elevated temperature, but not by dichloronitrophenol, indicated that this activity was due to a monoamine form of PST. Inhibition of the low-affinity reaction by dichloronitrophenol, but not by elevated temperature, indicated that this activity was due to a phenol form of PST. As a comparison, experiments with the rat liver cytosol demonstrated only one activity, with apparent KM values of 50 microM for both enantiomers and opposite stereoselectivity in maximum velocity compared to humans, {plus minus}-HOPS ratio 0.72. The results of this study demonstrate stereoselectivity in human hepatic sulfation of a chiral phenolic amine, with clear differences between PST isoenzymes.

  2. Asymmetric synthesis of functionalized cyclohexanes bearing five stereocenters via a one-pot organocatalytic Michael-Michael-1,2-addition sequence.

    PubMed

    Chauhan, Pankaj; Urbanietz, Gregor; Raabe, Gerhard; Enders, Dieter

    2014-07-04

    A highly stereoselective one-pot procedure involving an enantioselective Michael addition promoted by low loading of an amino-squaramide catalyst followed by an achiral base catalyzed domino Michael-Knoevenagel-type 1,2-addition sequence provides efficient access to fully substituted cyclohexanes bearing five contiguous stereogenic centers in good yields (68-86%) and excellent stereoselectivities (>30 : 1 dr and 96-99% ee).

  3. Synthesis of the aggregation pheromone of the Colorado potato beetle from its degradation product.

    PubMed

    Wacławczyk-Biedroń, Weronika; Frąckowiak-Wojtasek, Bożena; Strub, Daniel; Rzechak, Magdalena; Wojtasek, Hubert

    2015-09-01

    Incubation of the Colorado potato beetle aggregation pheromone, (S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one, with antennal or leg extracts from this beetle gave 6-methyl-5-hepten-2-one as the major product. This ketone was used as a substrate in a stereoselective synthesis of the pheromone. It was attached to the butanediacetal of glycolic acid with good stereoselectivity and the desired isomer was further enriched by purification of the product of this reaction on silica gel.

  4. Formal synthesis of (+)-3-epi-eupomatilone-6 and the 3,5-bis-epimer.

    PubMed

    Yodwaree, Sariya; Soorukram, Darunee; Kuhakarn, Chutima; Tuchinda, Patoomratana; Reutrakul, Vichai; Pohmakotr, Manat

    2014-09-21

    The formal synthesis of (+)-3-epi-eupomatilone-6 () and the 3,5-bis-epimer () has been accomplished. The key synthetic strategy involved the stereoselective construction of (3R,4S,5R)- and (3R,4S,5S)-trisubstituted γ-butyrolactones and from (2R,3R)-2,3-dimethyl-4-pentenoic acid derivative , which was readily obtained via stereoselective conjugate addition of vinylmagnesium chloride to a chiral α,β-unsaturated N-acyl oxazolidinone (Evans' auxiliary) followed by α-methylation.

  5. Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution

    NASA Astrophysics Data System (ADS)

    Kille, Sabrina; Zilly, Felipe E.; Acevedo, Juan P.; Reetz, Manfred T.

    2011-09-01

    A current challenge in synthetic organic chemistry is the development of methods that allow the regio- and stereoselective oxidative C-H activation of natural or synthetic compounds with formation of the corresponding alcohols. Cytochrome P450 enzymes enable C-H activation at non-activated positions, but the simultaneous control of both regio- and stereoselectivity is problematic. Here, we demonstrate that directed evolution using iterative saturation mutagenesis provides a means to solve synthetic problems of this kind. Using P450 BM3(F87A) as the starting enzyme and testosterone as the substrate, which results in a 1:1 mixture of the 2β- and 15β-alcohols, mutants were obtained that are 96-97% selective for either of the two regioisomers, each with complete diastereoselectivity. The mutants can be used for selective oxidative hydroxylation of other steroids without performing additional mutagenesis experiments. Molecular dynamics simulations and docking experiments shed light on the origin of regio- and stereoselectivity.

  6. A stereoselective esterase from Bacillus megaterium: purification, gene cloning, expression and catalytic properties.

    PubMed

    Zheng, Jian-Yong; Wang, Jian; Zhou, Sha-Sha; Li, Xiao-Jun; Ying, Xiang-Xian; Wang, Zhao

    2015-10-27

    Esterases (EC 3.1.1.X) have been used as biocatalysts due to their good stability, high chemo-, regio- and stereoselectivity. In our previous studies, Bacillus megaterium WZ009 harboring esterase displayed the unique capability to convert (S)-4-Chloro-3-hydroxyethylbutyrate (CHBE) in the racemate to (S)-3-hydroxy-γ-butyrolactone (HL) through stereoselective hydrolysis, dechlorination, and lactonization. The remaining (R)-CHBE and formed (S)-HL could be obtained in a one-pot enzymatic reaction. An esterase from B. megaterium WZ009 was purified and was found to have 466 encoded amino acids and an apparent molecular mass of 55 kDa. The purified esterase exhibited maximal activity at a temperature of 25 °C and at a pH of 11.5 towards 100 mM CHBE. When the stereoselective biocatalysis of rac-CHBE was performed using the recombinant Escherichia coli BL21 (DH3) cells harboring the esterase, the catalytic activity increased by 20-fold compared with the original strain B. megaterium WZ009. With the addition of activated carbon (62 g/L) in the reaction system, the conversion was increased from 39% to 45% at a substrate concentration of 750 mM. Another remarkable advantage is that both of the obtained residual (R)-CHBE and the formed (S)-HL had high optical purities (e.e.s > 99.9%, e.e.p > 99.9%), thereby making this esterase a usable biocatalyst for industrial application.

  7. Enolic schiff base aluminum complexes and their catalytic stereoselective polymerization of racemic lactide.

    PubMed

    Pang, Xuan; Du, Hongzhi; Chen, Xuesi; Wang, Xianhong; Jing, Xiabin

    2008-01-01

    A series of enolic Schiff base aluminum(III) complexes LAlR (where L=NNOO-tetradentate enolic Schiff base ligand) containing ligands that differ in their steric and electronic properties were synthesized. Their single crystals showed that these complexes are five-coordinated around the aluminum center. Their coordination geometries are between square pyramidal and trigonal bipyramidal. Their catalytic properties in the solution polymerization of racemic lactide (rac-LA) were examined. The modifications in the auxiliary ligand exhibited a dramatic influence on the catalytic performance. Lengthening the backbone from C(2) alkylene to C(3) alkylene resulted in remarkable enhancement of both the stereoselectivity and the polymerization rate because of the increasing flexibility of the diimine backbone. Electron-withdrawing substituents in the diketone also highly improved the activity and the stereoselectivity. Among these complexes, 4 b had the highest activity and the stereoselectivity owing to the C(3) alkylene backbone and the two gem-methyl groups on the middle carbon atom. The value of the polymerization rate constant (k(p)) catalyzed by 4 b in 70 degrees C was 1.90 L mol(-1) min(-1), the activation energy of the polymerization (35.4 kJ mol(-1)) was calculated according to the Arrhenius equation. Other factors that influenced the polymerization, such as the polymerization time, the temperature, and the monomer concentration, are also discussed in detail.

  8. Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution.

    PubMed

    Kille, Sabrina; Zilly, Felipe E; Acevedo, Juan P; Reetz, Manfred T

    2011-08-14

    A current challenge in synthetic organic chemistry is the development of methods that allow the regio- and stereoselective oxidative C-H activation of natural or synthetic compounds with formation of the corresponding alcohols. Cytochrome P450 enzymes enable C-H activation at non-activated positions, but the simultaneous control of both regio- and stereoselectivity is problematic. Here, we demonstrate that directed evolution using iterative saturation mutagenesis provides a means to solve synthetic problems of this kind. Using P450 BM3(F87A) as the starting enzyme and testosterone as the substrate, which results in a 1:1 mixture of the 2β- and 15β-alcohols, mutants were obtained that are 96-97% selective for either of the two regioisomers, each with complete diastereoselectivity. The mutants can be used for selective oxidative hydroxylation of other steroids without performing additional mutagenesis experiments. Molecular dynamics simulations and docking experiments shed light on the origin of regio- and stereoselectivity.

  9. Stereoselective degradation of benalaxyl in tomato, tobacco, sugar beet, capsicum, and soil.

    PubMed

    Gu, Xu; Wang, Peng; Liu, Donghui; Lv, Chunguang; Lu, Yuele; Zhou, Zhiqiang

    2008-02-01

    The stereoselective degradation of the racemic benalaxyl in vegetables such as tomato, tobacco, sugar beet, capsicum, and the soil has been investigated. The two enantiomers of benalaxyl in the matrix were extracted by organic solvent and determined by validated chiral high-performance liquid chromatography with a cellulose-tris-(3, 5-dimethylphenylcarbamate)-based chiral column. Rac-benalaxyl was fortified into the soil and foliar applied to vegetables. The assay method was linear over a range of concentrations (0.5-50 microg ml(-1)) and the mean recoveries in all the samples were more than 70% for the two enantiomers. The limit of detection for both enantiomers was 0.05 microg g(-1). The results in soil showed that R-(-)-enantiomer dissipated faster than S-(+)-enantiomer and the stereoselectivity might be caused by microorganisms. In tomato, tobacco, sugar, beet, and capsicum plants, there was significantly stereoselective metabolism. The preferential absorption and degradation of S-(+)-enantiomer resulted an enrichment of the R-(-)-enantiomer residue in all the vegetables.

  10. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids

    SciTech Connect

    Freneaux, E.; Fromenty, B.; Berson, A.; Labbe, G.; Degott, C.; Letteron, P.; Larrey, D.; Pessayre, D. , Hopital Beaujon, Clichy )

    1990-11-01

    The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of (1-{sup 14}C)palmitic acid but not that of (1-{sup 14}C)palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of (1-{sup 14}C)palmitic acid and markedly inhibited the beta oxidation of (1-{sup 14}C)octanoic acid and (1-{sup 14}C)butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of ({sup 14}C)CO{sub 2} from (1-{sup 14}C)fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids.

  11. Y(IO₃)₃ as a novel photocatalyst: synthesis, characterization, and highly efficient photocatalytic activity.

    PubMed

    Huang, Hongwei; He, Ying; He, Ran; Lin, Zheshuai; Zhang, Yihe; Wang, Shichao

    2014-08-04

    Nonbonding layer-structured Y(IO3)3 was successfully prepared by a simple hydrothermal route and investigated as a novel photocatalyst for the first time. Its crystal structure was characterized by X-ray diffraction, high-resolution transmission electron microscopy, and scanning electron microscopy. The optical absorption edge and band gap of Y(IO3)3 have been determined by UV-vis diffuse reflectance spectra. Theoretical calculations of the electronic structure of Y(IO3)3 confirmed its direct optical transition property near the absorption edge region, and the orbital components of the conduction band and valence band (VB) were also analyzed. The photocatalytic performance of Y(IO3)3 was evaluated by photooxidative decomposition of rhodamine B under ultraviolet light irradiation. It demonstrated that Y(IO3)3 exhibits highly efficient photocatalytic activity, which is much better than those of commercial TiO2 (P25) and important UV photocatalysts BiOCl and BiIO4. The origin of the excellent photocatalytic performance of Y(IO3)3 was investigated by electron spin resonance and terephthalic acid photoluminescence techniques. The results revealed that the highly strong photooxidation ability that resulted from its very positive VB position should be responsible for the excellent photocatalytic performance.

  12. Synthesis of Highly Uniform and Compact Lithium Zinc Ferrite Ceramics via an Efficient Low Temperature Approach.

    PubMed

    Xu, Fang; Liao, Yulong; Zhang, Dainan; Zhou, Tingchuan; Li, Jie; Gan, Gongwen; Zhang, Huaiwu

    2017-03-27

    LiZn ferrite ceramics with high saturation magnetization (4πMs) and low ferromagnetic resonance line widths (ΔH) represent a very critical class of material for microwave ferrite devices. Many existing approaches emphasize promotion of the grain growth (average size is 10-50 μm) of ferrite ceramics to improve the gyromagnetic properties at relatively low sintering temperatures. This paper describes a new strategy for obtaining uniform and compact LiZn ferrite ceramics (average grains size is ∼2 μm) with enhanced magnetic performance by suppressing grain growth in great detail. The LiZn ferrites with a formula of Li0.415Zn0.27Mn0.06Ti0.1Fe2.155O4 were prepared by solid reaction routes with two new sintering strategies. Interestingly, results show that uniform, compact, and pure spinel ferrite ceramics were synthesized at a low temperature (∼850 °C) without obvious grain growth. We also find that a fast second sintering treatment (FSST) can further improve their gyromagnetic properties, such as higher 4πMs and lower ΔH. The two new strategies are facile and efficient for densification of LiZn ferrite ceramics via suppressing grain growth at low temperatures. The sintering strategy reported in this study also provides a referential experience for other ceramics, such as soft magnetism ferrite ceramics or dielectric ceramics.

  13. Synthesis of magnetic metal-organic framework (MOF) for efficient removal of organic dyes from water

    PubMed Central

    Zhao, Xiaoli; Liu, Shuangliu; Tang, Zhi; Niu, Hongyun; Cai, Yaqi; Meng, Wei; Wu, Fengchang; Giesy, John P.

    2015-01-01

    A novel, simple and efficient strategy for fabricating a magnetic metal-organic framework (MOF) as sorbent to remove organic compounds from simulated water samples is presented and tested for removal of methylene blue (MB) as an example. The novel adsorbents combine advantages of MOFs and magnetic nanoparticles and possess large capacity, low cost, rapid removal and easy separation of the solid phase, which makes it an excellent sorbent for treatment of wastewaters. The resulting magnetic MOFs composites (also known as MFCs) have large surface areas (79.52 m2 g−1), excellent magnetic response (14.89 emu g−1), and large mesopore volume (0.09 cm3 g−1), as well as good chemical inertness and mechanical stability. Adsorption was not drastically affected by pH, suggesting π–π stacking interaction and/or hydrophobic interactions between MB and MFCs. Kinetic parameters followed pseudo-second-order kinetics and adsorption was described by the Freundlich isotherm. Adsorption capacity was 84 mg MB g−1 at an initial MB concentration of 30 mg L−1, which increased to 245 mg g−1 when the initial MB concentration was 300 mg L−1. This capacity was much greater than most other adsorbents reported in the literature. In addition, MFC adsorbents possess excellent reusability, being effective after at least five consecutive cycles. PMID:26149818

  14. Facile synthesis of cobalt-doped zinc oxide thin films for highly efficient visible light photocatalysts

    NASA Astrophysics Data System (ADS)

    Altintas Yildirim, Ozlem; Arslan, Hanife; Sönmezoǧlu, Savaş

    2016-12-01

    Cobalt-doped zinc oxide (Co:ZnO) thin films with dopant contents ranging from 0 to 5 at.% were prepared using the sol-gel method, and their structural, morphological, optical, and photocatalytic properties were characterized. The effect of the dopant content on the photocatalytic properties of the films was investigated by examining the degradation behavior of methylene blue (MB) under visible light irradiation, and a detailed investigation of their photocatalytic activities was performed by determining the apparent quantum yields (AQYs). Co2+ ions were observed to be substitutionally incorporated into Zn2+ sites in the ZnO crystal, leading to lattice parameter constriction and band gap narrowing due to the photoinduced carriers produced under the visible light irradiation. Thus, the light absorption range of the Co:ZnO films was improved compared with that of the undoped ZnO film, and the Co:ZnO films exhibited highly efficient photocatalytic activity (∼92% decomposition of MB after 60-min visible light irradiation for the 3 at.% Co:ZnO film). The AQYs of the Co:ZnO films were greatly enhanced under visible light irradiation compared with that of the undoped ZnO thin film, demonstrating the effect of the Co doping level on the photocatalytic activity of the films.

  15. Efficient synthesis and characterization of ergosterol laurate in a solvent-free system.

    PubMed

    He, Wen-Sen; Yin, Ji; Xu, Han-Shan; Qian, Qiu-Ying; Jia, Cheng-Sheng; Ma, Hai-Le; Feng, Biao

    2014-12-03

    Ergosterol and its derivatives have attracted much attention for a variety of health benefits, such as anti-inflammatory and antioxidant activities. However, ergosterol esters are advantageous because this compound has better solubility than the free ergosterol. In this work, ergosterol laurate was efficiently synthesized for the first time by direct esterification in a solvent-free system. The desired product was purified, characterized by Fourier transform infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance, and finally confirmed to be ergosterol laurate. Meanwhile, the effect of various catalysts, catalyst dose, reaction temperature, substrate molar ratio, and reaction time were studied. Both the conversion of ergosterol and the selectivity of the desired product can reach above 89% under the selected conditions: sodium dodecyl sulfate + hydrochloric acid as the catalyst, 2:1 molar ratio of lauric acid/ergosterol, catalyst dose of 4% (w/w), 120 °C, and 2 h. The oil solubility of ergosterol and its laurate was also compared. The results showed that the solubility of ergosterol in oil was significantly improved by direct esterification with lauric acid, thus greatly facilitating the incorporation into a variety of oil-based systems.

  16. Synthesis of magnetic biocomposite for efficient adsorption of azo dye from aqueous solution.

    PubMed

    Sivashankar, R; Sathya, A B; Krishnakumar, Uma; Sivasubramanian, V

    2015-11-01

    A novel magnetic biocomposite was synthesized using metal chlorides and aquatic macrophytes by co-precipitation method. The resulting product, magnetic biocomposite was characterized by Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX) and Scanning electron microscope (SEM). The adsorption performance of the magnetic biocomposite was tested with removal of Metanil Yellow dye from aqueous solution. The effect of influencing parameters such as initial dye concentration, solution pH and agitation were investigated. The equilibrium isotherm was well described by the Langmuir model with the with maximum adsorption capacity of 90.91mg/g. Adsorption kinetics experiments were carried out and the data were well fitted by a pseudo-second-order equation. The results revealed that the magnetic biocomposite could efficiently adsorb the azo dyes from aqueous solution, and the spent adsorbents could be recovered completely by magnetic separation process. Therefore, the prepared magnetic biocomposite could thus be used as promising adsorbent for the removal of azo dyes from polluted water.

  17. Synthesis, structural characterisation, bio-potential efficiency and DNA cleavage applications of nicotinamide metal complexes

    NASA Astrophysics Data System (ADS)

    Surendra Dilip, C.; Siva Kumar, V.; John Venison, S.; Vetha potheher, I.; Rajalaxmi (a) Subahashini, D.

    2013-05-01

    Mixed ligand complexes were synthesised using nicotinamide as the primary ligand and nitrite as the secondary ligand were characterised by FT-IR, UV-Vis, 1H NMR, TG-DTA-DTG, X-ray powder diffraction and physical analytical studies. From the molar conductance, magnetic moment and electronic spectral data of the synthesised complexes a general formula of [M(ONO)2(NA)2] where M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) and [Cr2(ONO)6(NA)2] with a distorted octahedral structure were proposed. Thermal analyses show that the complexes lose molecules of hydration initially and subsequently expel anionic and organic ligands in continuous steps. The kinetic parameter values, such as, E*, ΔH*, ΔS* and ΔG* illustrate the spontaneous association of the metal and ligands in the formation of the complexes. The antimicrobial efficacy of the ligand and its complexes were examined by in vitro method against various pathogenic bacterial and fungal strains. The metal complexes were found to posses efficient antimicrobial properties compared to nicotinamide and a few of these complexes could turn out to be excellent models for the design of effective antibiotic drug substances. The intercalating interaction of Cu(II) complex with CT-DNA was inspected by absorption spectral and viscosity studies, thermal denaturation and electro-analytical experiments.

  18. Synthesis and characterization of chitosan tripolyphosphate nanoparticles and its encapsulation efficiency containing Russell's viper snake venom.

    PubMed

    Venkatesan, C; Vimal, S; Hameed, A S Sahul

    2013-08-01

    Chitosan Tripolyphosphate (CS/TPP) nanoparticle is a biodegradable and nontoxic polysaccharide, used as a carrier for drug delivery. The morphology and particle-size measurements of the nanoparticles were studied by field emission scanning electron microscopy and Fourier Transform Infrared Spectroscopy (FTIR). This study aims to evaluate the impact of Russell's viper venom encapsulation on various factors and loading capacity, in addition to explore the physicochemical structure of nanoparticles. FTIR confirmed that tripolyphosphoric groups of TPP linked with ammonium groups of CS in the nanoparticles. Our results showed that CS can react with TPP to form stable cationic nanoparticles. The results also showed that encapsulation efficiency of venom at different concentrations of 20, 40, 60, 500, and 1000 µg/mL were achieved for CS/TPP nanoparticles at different concentrations of 1.5, 2, and 3 mg/mL. The cytotoxicity of CS/TPP nanoparticles was evaluated by MTT (-3 (4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole) assay.

  19. Self-templated synthesis of TiO2 hierarchical structure photocatalyst with high efficiency and good sedimentation property

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoning; Sang, Yuanhua; Yu, Xin; Liu, Baishan; Liu, Hong

    2016-10-01

    The balance between highly efficient photocatalysis and a good emulsion/water extraction property is crucial for the practical application of TiO2 photocatalysts. The TiO2 hierarchical structure was synthesized via a hydrothermal treatment of H2Ti3O7 nanobelts with TiF4. The hydrolysis of TiF4 supplies the TiO2 nucleus, and HF, which is derived from the hydrolysis process, acts as a corrosive to etch the H2Ti3O7 nanobelt, resulting in a dynamic dissolution and precipitation process. The etching process resulted in self-generated TiF4 and initiated hydrolysis to generate new TiO2 primary particles. Induced by F etching process, Ti3+ defects were formed in the hierarchical structures, which was beneficial to the photocatalytic property. This hydrolysis-etching-hydrolysis process allows for template dissolution and self-assembly of anatase TiO2 nanobelts to form the TiO2 hierarchical structures. This process balances the nanominiaturization and sedimentation property requirements by the photocatalytic and emulsion/water extraction properties. This simple hydrolysis-etching-hydrolysis process can be applied to the synthesis of many other hierarchical structures.

  20. Inspired by efficient cellulose-dissolving system: Facile one-pot synthesis of biomass-based hydrothermal magnetic carbonaceous materials.

    PubMed

    Ma, Jian-Feng; Xing, Jian-Xiong; Wang, Kun; Yang, Hai-Yan; Fei, Ben-Hua; Liu, Xing-E

    2017-05-15

    The core-shell structure of carbon encapsulated magnetic nanoparticles (CEMNs) displays unique properties. Enhancing the magnetization of iron core, in parallel, improving the encapsulation of carbon shell are the two major challenges in the synthesis of CEMNs. Inspired by efficient cellulose-dissolving system, carbon encapsulated magnetic nano-Fe3O4 particles (Fe3O4@C) with ∼10.0nm Fe3O4 cores and 1.9-3.3nm carbon shell, were successfully one-pot synthesized via a novel hydrothermal carbonization (HTC) process. The dissolving process in ionic liquids ([Emim]Ac and [Amim]Cl) completely cleaved the intra- and intermolecular H-bonds in cellulose, and favored the incorporation of Fe3O4 nanoparticles into the cellulose H-bonds systems during the regeneration process. Some stable linkages were formed in Fe3O4@C, taking Fe3O4 nanoparticles as a structure guiding agent. The morphology and properties of Fe3O4@C depended strongly on the type of carbon precursors and pyrolysis temperature. Well encapsulated nanostructure was obtained at HTC temperature 280°C, when [Emim]Ac-treated holocellulose was used as the carbon source. Meanwhile, the thickness of the amorphous shell and magnetization increased with HTC temperature. More importantly, a novel elements for understanding the growth mechanism for the Fe3O4@C composite under HTC conditions was proposed.