- Preparation of chiral β-hydroxytriazoles in one-pot chemoenzymatic bioprocesses catalyzed by Rhodotorula mucilaginosa
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Chemoenzymatic strategies for the preparation of enantiopure β-hydroxytriazoles were designed. These and other related compounds are particularly relevant because of their antitubercular bioactivities and as β-adrenergic receptor blockers. The ability of
- Aguirre-Pranzoni, Celeste,Tosso, Rodrigo D.,Bisogno, Fabricio R.,Kurina-Sanz, Marcela,Orden, Alejandro A.
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- Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade
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Enantioenriched azido alcohols are precursors for valuable chiral aziridines and 1,2-amino alcohols, however their chiral substituted analogues are difficult to access. We established a cascade for the asymmetric azidohydroxylation of styrene derivatives leading to chiral substituted 1,2-azido alcohols via enzymatic asymmetric epoxidation, followed by regioselective azidolysis, affording the azido alcohols with up to two contiguous stereogenic centers. A newly isolated two-component flavoprotein styrene monooxygenase StyA proved to be highly selective for epoxidation with a nicotinamide coenzyme biomimetic as a practical reductant. Coupled with azide as a nucleophile for regioselective ring opening, this chemo-enzymatic cascade produced highly enantioenriched aromatic α-azido alcohols with up to >99% conversion. A bi-enzymatic counterpart with halohydrin dehalogenase-catalyzed azidolysis afforded the alternative β-azido alcohol isomers with up to 94% diastereomeric excess. We anticipate our biocatalytic cascade to be a starting point for more practical production of these chiral compounds with two-component flavoprotein monooxygenases.
- Franssen, Maurice C. R.,Hollmann, Frank,Martínez-Montero, Lía,Paul, Caroline E.,Süss, Philipp,Schallmey, Anett,Tischler, Dirk
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p. 5077 - 5085
(2021/08/16)
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- A Straightforward Deracemization of sec-Alcohols Combining Organocatalytic Oxidation and Biocatalytic Reduction
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An efficient organocatalytic oxidation of racemic secondary alcohols, mediated by sodium hypochlorite (NaOCl) and 2-azaadamantane N-oxyl (AZADO), has been conveniently coupled with a highly stereoselective bioreduction of the intermediate ketone, catalyzed by ketoreductases, in aqueous medium. The potential of this one-pot two-step deracemization process has been proven by a large set of structurally different secondary alcohols. Reactions were carried out up to 100 mm final concentration enabling the preparation of enantiopure alcohols with very high isolated yields (up to 98 %). When the protocol was applied to the stereoisomeric rac/meso mixture of diols, these were obtained with very high enantiomeric excesses and diastereomeric ratios (95 % yield, >99 % ee, >99: 1 dr).
- Liardo, Elisa,Ríos-Lombardía, Nicolás,Morís, Francisco,González-Sabín, Javier,Rebolledo, Francisca
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p. 3031 - 3035
(2018/06/27)
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- Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents
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Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.
- Aratikatla, Eswar K.,Valkute, Tushar R.,Puri, Sunil K.,Srivastava, Kumkum,Bhattacharya, Asish K.
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supporting information
p. 1089 - 1105
(2017/08/03)
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- Stereoselective reduction of 2-azido-1-phenylethanone derivatives by whole cells of marine-derived fungi applied to synthesis of enantioenriched β-hydroxy-1,2,3-triazoles
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Several marine-derived fungi were evaluated by the bioreduction of 2-azido-1-phenylethanone 1, and the strains A. sydowii CBMAI 935 and M. racemosus CBMAI 847 were selected for the reduction of 2-azido-1-phenylethanone derivatives 2–4. Whole cells of A. s
- Alvarenga, Natália,Porto, André L. M.
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p. 388 - 396
(2017/10/06)
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- Chiral Crystalline Sponges for the Absolute Structure Determination of Chiral Guests
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Chiral crystalline sponges with preinstalled chiral references were synthesized. On the basis of the known configurations of the chiral references, the absolute structures of guest compounds absorbed in the pores of the crystalline sponges can be reliably
- Yan, Kaking,Dubey, Ritesh,Arai, Tatsuhiko,Inokuma, Yasuhide,Fujita, Makoto
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p. 11341 - 11344
(2017/08/30)
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- Azidolysis of epoxides catalysed by the halohydrin dehalogenase from Arthrobacter sp. AD2 and a mutant with enhanced enantioselectivity: an (S)-selective HHDH
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Halohydrin dehalogenase from Arthrobacter sp. AD2 catalysed azidolysis of epoxides with high regioselectivity and low to moderate (S)-enantioselectivity (E?=?1–16). Mutation of the asparagine 178 to alanine (N178A) showed increased enantioselectivity towards styrene oxide derivatives and glycidyl ethers. Conversion of aromatic epoxides was catalysed by HheA-N178A with complete enantioselectivity, however the regioselectivity was reduced. As a result of the enzyme-catalysed reaction, enantiomerically pure (S)-β-azido alcohols and (R)-α-azido alcohols (ee???99%) were obtained.
- Mikleu?evi?, Ana,Primo?i?, Ines,Hrenar, Tomica,Salopek-Sondi, Branka,Tang, Lixia,Elenkov, Maja Majeri?
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p. 930 - 935
(2016/09/13)
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- One-pot combination of enzyme and Pd nanoparticle catalysis for the synthesis of enantiomerically pure 1,2-amino alcohols
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One-pot combinations of sequential catalytic reactions can offer practical and ecological advantages over classical multi-step synthesis schemes. In this context, the integration of enzymatic and chemo-catalytic transformations holds particular potential for efficient and selective reaction sequences that would not be possible using either method alone. Here, we report the one-pot combination of alcohol dehydrogenase-catalysed asymmetric reduction of 2-azido ketones and Pd nanoparticle-catalysed hydrogenation of the resulting azido alcohols, which gives access to both enantiomers of aromatic 1,2-amino alcohols in high yields and excellent optical purity (ee >99%). Furthermore, we demonstrate the incorporation of an upstream azidolysis and a downstream acylation step into the one-pot system, thus establishing a highly integrated synthesis of the antiviral natural product (S)-tembamide in 73% yield (ee >99%) over 4 steps. Avoiding the purification and isolation of intermediates in this synthetic sequence leads to an unprecedentedly low ecological footprint, as quantified by the E-factor and solvent demand.
- Schrittwieser, Joerg H.,Coccia, Francesca,Kara, Selin,Grischek, Barbara,Kroutil, Wolfgang,D'Alessandro, Nicola,Hollmann, Frank
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p. 3318 - 3331
(2013/12/04)
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- Chemoenzymatic resolution of β-azidophenylethanols by candida antarctica and their application for the synthesis of chiral benzotriazoles
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As resoluc?o?es cine?ticas de (±)-β- azidofeniletano?is foram realizadas usando a lipase de Candida antarctica fornecendo os compostos enantiomericamente enriquecidos, (R)-β- azidofeniletano?is e acetato de (S)-β-azidofeniletila em bons excessos enantiome
- Rocha, Lenilson C.,Rosset, Isac G.,Melgar, Gliseida Z.,Raminelli, Cristiano,Porto, Andre? L. M.,Jeller, Alex H.
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p. 1427 - 1432
(2013/09/24)
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- Non-enzymatic kinetic resolution of 1,2-azidoalcohols using a planar-chiral DMAP derivative catalyst
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Optically pure 1,2-azidoalcohols are widely used as precursors for other high value organic products. A non-enzymatic kinetic resolution procedure for the stereoselective synthesis of chiral 1,2-azidoalcohols from the readily available racemic counterpart
- Mesas-Sánchez, Laura,Díaz-álvarez, Alba E.,Dinér, Peter
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p. 753 - 757
(2013/07/27)
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- Coupling biocatalysis and click chemistry: One-pot two-step convergent synthesis of enantioenriched 1,2,3-triazole-derived diols
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A fully convergent one-pot two-step synthesis of different chiral 1,2,3-triazole-derived diols in high yields and excellent enantio- and diastereoselectivities has been achieved under very mild conditions in aqueous medium by combining a single alcohol dehydrogenase (ADH) with a Cu-catalysed 'click' reaction. The Royal Society of Chemistry 2013.
- Cuetos, Aníbal,Bisogno, Fabricio R.,Lavandera, Iván,Gotor, Vicente
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p. 2625 - 2627
(2013/04/23)
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- Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: Highly enantioselective synthesis of valuable alcohols
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In the presence of PhSiH3 as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)2·H 2O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9 % enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10 000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98 % ee) and exceedingly high turn-over rates (up to 50 000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.
- Yu, Feng,Zhou, Ji-Ning,Zhang, Xi-Chang,Sui, Yao-Zong,Wu, Fei-Fei,Xie, Lin-Jie,S. C. Chan, Albert,Wu, Jing
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p. 14234 - 14240
(2012/01/12)
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- Ketone-alcohol hydrogen-transfer equilibria: Is the biooxidation of halohydrins blocked?
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To ensure the quasi-irreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen-transfer (HT) fashion, stoichiometric amounts of a-halo carbonyl compounds have been employed as hydrogen acceptors. The reason that these substrates lead to quasi-quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. To provide a clear rationale for this behavior, we investigate herein the redox equilibrium of a selected series of ketones and 2-propanol by undertaking a study that combines experimental and theoretical approaches. First, the activity of the (R)-specific alcohol dehydrogenase from Lactobacillus brevis (LBADH) with these substrates was studied. The docking of acetophenone/(R)-l-phenyethanol and a-chloroacetophenone/(S)-2-chloro- lphenylethanol in the active site of the enzyme confirms that there seems to be no structural reason for the lack of reactivity of halohydrins. This assumption is confirmed by the fact that the corresponding aluminum-catalyzed Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions afford similar conversions to those obtained with LBADH, showing that the observed reactivity is independent of the catalyst employed. While the initial rates of the enzymatic reductions and the IR v(C=0) values contradict the general belief that electron-withdrawing groups increase the electrophilicity of the carbonyl group, the calculated βG values of the isodesmic redox transformations of these series of ketones/alcohols with 2-propanol/acetone support the thermodynamic control of the reaction. As a result, a general method to predict the degree of conversion obtained in the HT-reduction process of a given ketone based on the IR absorption band of the carbonyl group is proposed, and a strategy to achieve the HT oxidation of halohydrins is also shown.
- Bisogno, Fabricio R.,Garcia-Urdiales, Eduardo,Valdes, Haydee,Lavandera, Ivan,Kroutil, Wolfgang,Suarez, Dimas,Gotor, Vicente
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supporting information; experimental part
p. 11012 - 11019
(2010/11/18)
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- One pot 'click' reactions: Tandem enantioselective biocatalytic epoxide ring opening and [3+2] azide alkyne cycloaddition
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Halohydrin dehalogenase (HheC) can perform enantioselective azidolysis of aromatic epoxides to 1,2-azido alcohols which are subsequently ligated to alkynes producing chiral hydroxy triazoles in a one-pot procedure with excellent enantiomeric excess. The Royal Society of Chemistry 2010.
- Campbell-Verduyn, Lachlan S.,Szymanski, Wiktor,Postema, Christiaan P.,Dierckx, Rudi A.,Elsinga, Philip H.,Janssen, Dick B.,Feringa, Ben L.
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supporting information; experimental part
p. 898 - 900
(2010/06/12)
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- Enantioselective reduction of α-substituted ketones mediated by the boronate ester TarB-NO2
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A facile and mild reduction procedure is reported for the preparation of chiral secondary alcohols prepared from α-substituted ketones using sodium borohydride and the chiral boronate ester (l)-TarB-NO2. Direct reduction of substituted ketones bearing Lewis basic heteroatoms generally provided secondary alcohols of only modest enantiomeric excess likely due to either competition between the target carbonyl and the functionalized sidechains at the Lewis acidic boron atom in TarB-NO2 or the added steric bulk of the α-sidechain. As an alternative method, these substrates were synthesized using TarB-NO2 via a two-step procedure involving the reduction of an α-halo ketone to a chiral terminal epoxide, followed by regioselective/regiospecific epoxide opening by various nucleophiles. This procedure provides access to a variety of functionalized secondary alcohols including β-hydroxy ethers, thioethers, nitriles, and amines with enantiomeric excesses of 94% and yields up to 98%.
- Eagon, Scott,Ball-Jones, Nicholas,Haddenham, Dustin,Saavedra, Jaime,Delieto, Cassandra,Buckman, Matthew,Singaram, Bakthan
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supporting information; experimental part
p. 6418 - 6421
(2010/12/30)
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- Intramolecular azide-alkyne [3 + 2] cycloaddition: Versatile route to new heterocyclic structural scaffolds
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Investigating the relatively unexplored intramolecular version of the azide-alkyne [3 + 2] cycloaddition, the present studies demonstrate the utility of the above reaction in the synthesis of a variety of as yet unreported heterocyclic structural scaffolds. The approach involved initial installation of strategic azide and alkyne moieties on a common structural framework, followed by their intramolecular cycloaddition studies. The pivotal azidoalkyne intermediates were efficiently accessed from a variety of easily available starting materials such as olefins, epoxides, amino acids, amino alcohols, ketones etc. The key reactions for incorporation of the azide functionality into the desired framework involved azidolysis of epoxides, displacement of hydroxy groups with azide nucleophiles, and diazo transfer on amine. Attachment of the desired alkyne functionalities was accomplished by either N-, or, O-alkylation with appropriate propargylic halides. The azidoalkynes thus prepared underwent smooth intramolecular cycloaddition, resulting in a variety of novel triazolooxazine and triazolopyrazine derivatives. Interestingly, unlike in the intermolecular version, metal catalysis was not necessary for the performance of the above cycloadditions. It is expected that the results from the present studies and its further extension will provide a potentially fertile pathway to a variety of unique chemical entities of structural and biological significance.
- Li, Rongti,Jansen, Daniel J.,Datta, Apurba
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experimental part
p. 1921 - 1930
(2009/06/28)
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- Synthesis of optically pure 2-azido-1-arylethanols with isolated enzymes and conversion to triazole-containing β-blocker analogues employing click chemistry
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(Chemical Equation Presented) Both antipodes of 2-azido-1-arylethanols were synthesized with excellent optical purity via enzymatic reduction of the corresponding α-azidoacetophenone derivatives catalyzed by a recombinant carbonyl reductase from Candida m
- Ankati, Haribabu,Yang, Yan,Zhu, Dunming,Biehl, Edward R.,Hua, Ling
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p. 6433 - 6436
(2008/12/22)
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- Enzymatic process for the preparation of optically active alcohols from ketones using tuberous root Daucus carota
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The present invention relates to an enzymatic process for the preparation of optically active chiral alcohols using tuberous root Daucus carota; particularly invention relates to an enzymatic process for the preparation of optically active alcohols by enantioselective reduction of corresponding ketones using tuberous root Daucus carota.
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Page/Page column 10
(2008/06/13)
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- Biocatalytic deuterium- and hydrogen-transfer using over-expressed ADH-'A': Enhanced stereoselectivity and 2H-labeled chiral alcohols
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Employing the over-expressed highly organic solvent tolerant alcohol dehydrogenase ADH-'A' from Rhodococcus ruber DSM 44541, versatile building blocks, which were not accessible by the wild type catalyst, were obtained in > 99% e.e.; furthermore, employing d8-2-propanol as deuterium source, stereoselective biocatalytic deuterium transfer was made feasible to furnish enantiopure deuterium labeled sec-alcohols on a preparative scale employing a single enzyme. The Royal Society of Chemistry 2006.
- Edegger, Klaus,Gruber, Christian C.,Poessl, Tina M.,Wallner, Sabine R.,Lavandera, Ivan,Faber, Kurt,Niehaus, Frank,Eck, Juergen,Oehrlein, Reinhold,Hafner, Andreas,Kroutil, Wolfgang
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p. 2402 - 2404
(2008/03/28)
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- Synthesis of enantiopure β-azidoalcohols from their ketoazides by reduction with NaBH4 in the presence of alumina and in situ lipase resolution
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An enantioselective synthesis of chiral β-azidoalcohols via the reduction of the corresponding ketoazides with NaBH4 in the presence of moist aluminium oxide followed by an in situ lipase-mediated resolution is described. The efficiency of vari
- Kamal, Ahmed,Shaik, Ahmad Ali,Sandbhor, Mahendra,Malik, M. Shaheer
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p. 935 - 939
(2007/10/03)
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- Stereoselective acylations of 1,2-azidoalcohols with vinyl acetate, catalyzed by lipase Amano PS
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Lipase PS-catalyzed kinetic resolution of vicinal azidoalcohols was accomplished. The enzymatic reaction rates and the enantioselectivities were significantly enhanced under the ultrasonic irradiation.
- Brenelli, Eugenia Cristina Souza,Fernandes, Jane Luiza Nogueira
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p. 1255 - 1259
(2007/10/03)
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- Practical synthesis of optically active amino alcohols via asymmetric transfer hydrogenation of functionalized aromatic ketones
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2-Substituted acetophenones such as 2-cyano-, 2-azido-, or 2-nitroacetophenones were effectively reduced with a mixture of HCOOH/N(C2H5)3 containing a chiral Ru(II) catalyst, RuCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine](p-cymene), giving the corresponding optically active alcohols, which can be converted to optically active amino alcohols with excellent ee's. Similarly, the reaction of 2-benzoylacetophenone with the same Ru catalyst gave a quantitative yield of the corresponding optically active 1,3-diol with 99% ee.
- Watanabe, Masahito,Murata, Kunihiko,Ikariya, Takao
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p. 1712 - 1715
(2007/10/03)
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- Efficient enantioselective reduction of ketones with Daucus carota root
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A novel and efficient reduction of various prochiral ketones such as acetopehones, α-azido aryl ketones, β-ketoesters, and aliphatic acyclic and cyclic ketones to the corresponding optically acive secondary alcohols with moderate to excellent chemical yield was achieved by using Daucus carota, root plant cells under extremely mild and environmentally benign conditions in aqueous medium, has been described. Many of these optically active alcohols are the potential chiral building blocks for the synthesis of pharmaceutically important molecules and asymmetric chiral ligands. Hence, this biocatalytic approach is found to be the most suitable for the preparation of a wide range of chiral alcohols and gave inspiration for the development of a new biotechnological process.
- Yadav,Nanda,Thirupathi Reddy,Bhaskar Rao
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p. 3900 - 3903
(2007/10/03)
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- Highly enantioselective and regioselective biocatalytic azidolysis of aromatic epoxides
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(equation presented) The halohydrin dehalogenase from Agrobacterium radiobacter AD1 catalyzed the highly enantioselective and β-regioselective azidolysis of (substituted) styrene oxides. By means of kinetic resolutions the remaining epoxide and the formed azido alcohol could be obtained in very high ee. In a large scale conversion, the decrease in yield and selectivity due to the uncatalyzed chemical side reaction could be overcome by slow addition of azide.
- Spelberg, Jeffrey H. Lutje,Van Vlieg, Johan E. T. Hylckama,Tang, Lixia,Janssen, Dick B.,Kellogg, Richard M.
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- A facile synthesis of (R)-(-)-2-azido-1-arylethanols from 2-azido-1-arylketones using baker's yeast
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A novel and efficient stereoselective reduction of 2-azido-1-aryl ketones using baker's yeast is described.
- Yadav,Reddy, P. Thirupathi,Nanda, Samik,Rao, A. Bhaskar
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- A New Stereochemical Model from NMR for Benzoylated Cyclodextrins, Promising New Chiral Solvating Agents for the Chiral Analysis of 3,5-Dinitrophenyl Derivatives
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Hexakis(2,3-di-O-benzoyl)-α-cyclodextrin and hexakis(2,3,6-tri-O-benzoyl)-α-cyclodextrin have been employed as chiral solvating agents (CSAs) for the NMR determination of the enantiomeric composition of derivatives of chiral amines, amino alcohols, alcohols, carboxyl acids, and amino acids bearing a 3,5-dinitrophenyl moiety. The conformational features of the two cyclodextrins have been carefully analyzed by NMR spectroscopy, and the origin of the symmetry change (C6 → C3), detected by NMR for hexakis(2,3-di-O-benzoyl)-α-cyclodextrin in CDC13, has been clarified.
- Uccello-Barretta, Gloria,Cuzzola, Angela,Balzano, Federica,Menicagli, Rita,Iuliano, Anna,Salvadori, Piero
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p. 827 - 835
(2007/10/03)
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- Rationally designed 'dipeptoid' analogues of cholecystokinin (CCK): C-terminal structure-activity relationships of α-methyl tryptophan derivatives
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This paper outlines the synthesis and C-terminal structure-activity relationships (SAR) of a series of α-methyl tryptophanylphenethylamide analogues of the neuropeptide cholecystokinin (CCK).CCK-B and CCK-A receptor binding affinities of these analogues are described and the contributions of the various side chains on the phenethylamide moiety to binding affinity are discussed.Several of the compounds prepared have CCK-B receptor binding affinities similar to that found with the endogenous neuropeptide CCK-26-33 (sulphated) (CCK-B, IC50 = 0.3 nM) and are highly selective over the CCK-A receptor.Amongst the most potent of the compounds synthesized are *,S*)>-β-3,7>dec-2-yloxy)carbonyl>amino>propyl>amino>benzenebutanoic acid 22, *,S*)>-3,7>dec-2-yloxy)carbonyl>amino>propyl>amino>-3-phenylpropyl>thio>acetic acid 28a and *,S*)>-3,7>dec-2-yloxy)carbonyl>amino>propyl>amino>-3-phenylpropyl>sulfonyl>acetic acid 32 which have CCK-B receptor binding affinities of IC50 = 0.3, 0.3 and 0.2 nM with CCK-A/B ratios of 220, 700 and 1000, respectively.CCK-B receptor selective ligands, 22, 28a and 32 were also shown to be potent anatagonists in blocking pentagastrin-evoked excitation in neurons of the rat hypothalamic ventro-medial nucleus (VMN) with the Ke values of 2.8, 23 and 5.9 nM, respectively. Keywords: cholecystokinin / dipeptoid analogues / structure-affinity relationships / α-methyl-tryptophan derivatives / C-terminal
- Boden, P. R.,Eden, J. M.,Higginbottom, M.,Hill, D. R.,Horwell, D. C.,et al.
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- Enantioselective catalytic reductions of ketones with new four membered oxazaborolidines: Application to (S)-tetramisole
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Enantioselective catalytic reduction of ketones with both the enantiomers of new four membered oxazaborolidines is described.
- Rama Rao,Gurjar,Kaiwar
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p. 859 - 862
(2007/10/02)
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- SELECTIVE RING-OPENING REACTION OF STYRENE OXIDE WITH LITHIUM AZIDE IN THE PRESENCE OF CYCLODEXTRINS IN AQUEOUS MEDIA
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Regioselective ring-opening of racemic styrene oxide was achieved by lithium azide in the presence of β-cyclodextrin in aqueous media.Kinetic resolution of racemic epoxide was observed and 1-phenyl-2-azido-ethanol was obtained with 78 percent ee.
- Guy, Alain,Doussot, Joel,Garreau, Robert,Godefroy-Falguieres, Annie
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p. 247 - 250
(2007/10/02)
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- Enantioselective synthesis of (R)-(-)-1-phenylethanolamines using Baker's yeast reduction of some α-substituted methyl phenyl ketones
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The Baker's yeast reductions of α-chloroacetophenone, α-azidoacetophenone and 2-oxo-2-phenylacetamide are used as key steps in the preparation of optically active (R)-(-)-1-phenylethanolamines.
- Brenelli, Eugenia C S,Carvalho, Marcia de,Okubo, Marina T,Marques, Margarete,Moran, Paulo J S,et al.
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p. 821 - 823
(2007/10/02)
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