scholarly journals Efficient Biocatalytic Preparation of Optically Pure (R)-1-[4-(Trifluoromethyl)phenyl]ethanol by Recombinant Whole-Cell-Mediated Reduction

Catalysts ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 391 ◽  
Author(s):  
Ying Chen ◽  
Nana Xia ◽  
Yuewang Liu ◽  
Pu Wang
Keyword(s):  
Organic Solvent ◽  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
Aqueous System ◽  
Cell Membrane Permeability ◽  
Buffer Solution ◽  
Preparative Scale ◽  
Buffer Medium ◽  
Polar Organic Solvent ◽  
Optically Pure

(R)-1-[4-(Trifluoromethyl)phenyl]ethanol is an important pharmaceutical intermediate of a chemokine CCR5 antagonist. In the present study, a bioprocess for the asymmetric reduction of 4-(trifluoromethyl)acetophenone to (R)-1-[4-(trifluoromethyl)phenyl]ethanol was developed by recombinant Escherichia coli cells with excellent enantioselectivity. In order to overcome the conversion limitation performed in the conventional buffer medium resulting from poor solubility of non-natural substrate, we subsequently established a polar organic solvent-aqueous medium to improve the efficacy. Isopropanol was selected as the most suitable cosolvent candidate, based on the investigation on a substrate solubility test and cell membrane permeability assay in different organic solvent-buffer media. Under the optimum conditions, the preparative-scale asymmetric reduction generated a 99.1% yield with >99.9% product enantiomeric excess (ee) in a 15% (v/v) isopropanol proportion, at 100 mM of 4-(trifluoromethyl)acetophenone within 3 h. Compared to bioconversion in the buffer medium, the developed isopropanol-aqueous system enhanced the substrate concentration by 2-fold with a remarkably improved yield (from 62.5% to 99.1%), and shortened the reaction time by 21 h. Our study gave the first example for a highly enantioselective production of (R)-1-[4-(trifluoromethyl)phenyl]ethanol by a biological method, and the bioreduction of 4-(trifluoromethyl)acetophenone in a polar organic solvent-aqueous system was more efficient than that in the buffer solution only. This process is also scalable and has potential in application.

scholarly journals Calcium(II)-mediated resolution of methyl o-chloromandelate with chiral O,O′-dibenzoyltartaric acid in preparative scale

2019 ◽  
Vol 42 (1) ◽  
pp. 19-22
Author(s):  
Hong-Wu Xu ◽  
Li-Huan Wu ◽  
Qiang Ren ◽  
Cui-Yu Liu ◽  
Guan-Qing Yan
Keyword(s):  
Mother Liquor ◽  
Enantiomeric Excess ◽  
Ethanol Solution ◽  
Preparative Scale ◽  
Mixed Ligands ◽  
Excess Value ◽  
Optically Pure

Abstract We report here the coordination-mediated resolution of methyl o-chloromandelate, which is a key intermediate for clopidogrel, in preparative scale. The reaction of CaO, optically pure (2R, 3R)-O,O′-dibenzoyltartaric acid, and methyl o-chloromandelate in ethanol solution afforded a mixed-ligands calcium(II) complex that was further purified by stirring of the crystals in hot methanol. Methyl (R)-o-chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (71%) by treatment of the complex with acid. At the same time, (2R, 3R)-O,O′-dibenzoyltartaric acid was recovered in 72% yield. In addition, methyl (S)-o-chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (73%) by recovery from the mother liquor and resolution with the same procedure for methyl (R)-o-chloromandelate, except that (2S, 3S)-O,O′-dibenzoyltartaric acid was used as the resolving reagent.

scholarly journals Yeast-Mediated Stereoselective Reduction of α-Acetylbutyrolactone

2018 ◽  
Vol 8 (8) ◽  
pp. 1334 ◽  
Author(s):  
Wanda Mączka ◽  
Katarzyna Wińska ◽  
Małgorzata Grabarczyk ◽  
Barbara Żarowska
Keyword(s):  
Organic Solvent ◽  
Yarrowia Lipolytica ◽  
Enantiomeric Excess ◽  
Deep Eutectic Solvent ◽  
Ester Group ◽  
Resting Cells ◽  
Media Composition ◽  
Yeast Strains ◽  
Optically Pure ◽  
Diastereomeric Excess

α’-1’-Hydroxyethyl-γ-butyrolactone—a product of reduction of α-acetylbutyrolactone possesses two stereogenic centres and two reactive functionalities (an alcohol and an ester group). Additionally, this compound has a similar structure to γ-butyrolactone (GBL) which is psychoactive. In the present work, biotransformation using seven yeast strains was used to obtain anti stereoisomers of α’-1’-hydroxyethyl-γ-butyrolactone. The process was carried out in both growing and resting culture. The effect of media composition and organic solvent addition on stereoselectivity and effectiveness of biotransformation was also studied. After one day of transformation, optically pure (3R,1’R)-hydroxylactone was obtained by means of Yarrowia lipolytica P26A in YPG medium (yeast extract (1%), peptone (2%) and glucose (2%)). In turn, the use of resting cells culture of Candida viswanathi AM120 in the presence of 10% DES (deep eutectic solvent) allowed us to obtain a (3S,1’S)-enantiomer with de = 85% (diastereomeric excess) and ee 76% (enantiomeric excess).

scholarly journals Bienzymatic Cascade for the Synthesis of an Optically Active O-benzoyl Cyanohydrin

Catalysts ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 522 ◽  
Author(s):  
Laura Leemans ◽  
Luuk van Langen ◽  
Frank Hollmann ◽  
Anett Schallmey
Keyword(s):  
Organic Solvent ◽  
Manihot Esculenta ◽  
Direct Synthesis ◽  
Enantiomeric Excess ◽  
Candida Antarctica ◽  
Optically Active ◽  
Candida Antarctica Lipase ◽  
Hydroxynitrile Lyase ◽  
Lipase A ◽  
Optically Pure

A concurrent bienzymatic cascade for the synthesis of optically pure (S)-4-methoxymandelonitrile benzoate ((S)-3) starting from 4-anisaldehyde (1) has been developed. The cascade involves an enantioselective Manihot esculenta hydroxynitrile lyase-catalyzed hydrocyanation of 1, and the subsequent benzoylation of the resulting cyanohydrin (S)-2 catalyzed by Candida antarctica lipase A in organic solvent. To accomplish this new direct synthesis of the protected enantiopure cyanohydrin, both enzymes were immobilized and each biocatalytic step was studied separately in search for a window of compatibility. In addition, potential cross-interactions between the two reactions were identified. Optimization of the cascade resulted in 81% conversion of the aldehyde to the corresponding benzoyl cyanohydrin with 98% enantiomeric excess.

scholarly journals Chemoenzymatic access to enantiopure N-containing furfuryl alcohol from chitin-derived N-acetyl-D-glucosamine

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Ya-Cheng Hao ◽  
Min-Hua Zong ◽  
Zhi-Lin Wang ◽  
Ning Li
Keyword(s):  
Enzyme Catalysis ◽  
Furfuryl Alcohol ◽  
Asymmetric Reduction ◽  
Streptomyces Coelicolor ◽  
Enantiomeric Excess ◽  
Rare Sugar ◽  
Preparative Scale ◽  
Step Process ◽  
Chemical Catalysis ◽  
Acid Catalyzed

Abstract Background Chiral furfuryl alcohols are important precursors for the synthesis of valuable functionalized pyranones such as the rare sugar L-rednose. However, the synthesis of enantiopure chiral biobased furfuryl alcohols remains scarce. In this work, we present a chemoenzymatic route toward enantiopure nitrogen-containing (R)- and (S)-3-acetamido-5-(1-hydroxylethyl)furan (3A5HEF) from chitin-derived N-acetyl-D-glucosamine (NAG). Findings 3-Acetamido-5-acetylfuran (3A5AF) was obtained from NAG via ionic liquid/boric acid-catalyzed dehydration, in an isolated yield of approximately 31%. Carbonyl reductases from Streptomyces coelicolor (ScCR) and Bacillus sp. ECU0013 (YueD) were found to be good catalysts for asymmetric reduction of 3A5AF. Enantiocomplementary synthesis of (R)- and (S)-3A5HEF was implemented with the yields of up to  >  99% and the enantiomeric excess (ee) values of  >  99%. Besides, biocatalytic synthesis of (R)-3A5HEF was demonstrated on a preparative scale, with an isolated yield of 65%. Conclusions A two-step process toward the chiral furfuryl alcohol was successfully developed by integrating chemical catalysis with enzyme catalysis, with excellent enantioselectivities. This work demonstrates the power of the combination of chemo- and biocatalysis for selective valorization of biobased furans. Graphic abstract

Micellization in Water-Polar Organic Solvent Binary Mixtures

2011 ◽  
Vol 1 (4) ◽  
pp. 352-368
Author(s):  
Maria Luisa Moya ◽  
Maria del Mar Graciani/snm ◽  
> ◽  
Victoria Isabel Martin
Keyword(s):  
Organic Solvent ◽  
Binary Mixtures ◽  
Polar Organic Solvent

scholarly journals Coordination-Driven Poly[2]Pseudorotaxanes in Highly Polar Organic Solvent

2020 ◽  
Vol 8 ◽  
Author(s):  
Hang Su ◽  
Wei Chen ◽  
Liang Li ◽  
Bin Li ◽  
Zhi-Yuan Zhang ◽  
...  
Keyword(s):  
Organic Solvent ◽  
Polar Organic Solvent

Enzymes in organic synthesis. 33. Stereoselective pig liver esterase-catalyzed hydrolyses of meso cyclopentyl-, tetrahydrofuranyl-, and tetrahydrothiophenyl-1,3-diesters

1985 ◽  
Vol 63 (2) ◽  
pp. 452-456 ◽  
Author(s):  
J. Bryan Jones ◽  
R. Scott Hinks ◽  
Philip G. Hultin
Keyword(s):  
Organic Synthesis ◽  
Absolute Configuration ◽  
Enantiomeric Excess ◽  
Membered Ring ◽  
Pig Liver ◽  
Pig Liver Esterase ◽  
Preparative Scale ◽  
Liver Esterase ◽  
The Absolute ◽  
Enzymes In Organic Synthesis

Preparative-scale pig liver esterase-catalyzed hydrolyses of five-membered ring meso-1,3-diesters are enantiotopically selective. While pro-S enantiotopic selectivity is exhibited in each case, the absolute configuration sense of the hydrolysis in the cyclopentyl series is opposite to that of both the tetrahydrofuranyl and tetrahydrothiophenyl diesters. The enantiomeric excess levels induced are in the 34–46% range.

Practical Synthesis of Optically Pure Methyl (2R,3S)-2,3-Epoxybutanoate via Microbial Asymmetric Reduction of α-Chloroacetoacetate

Synthesis ◽  
1993 ◽  
Vol 1993 (05) ◽  
pp. 513-516 ◽  
Author(s):  
Hiroyuki Akita ◽  
Reiko Todoroki ◽  
Hiroshi Endo ◽  
Yoshinobu Ikari ◽  
Takeshi Oishi
Keyword(s):  
Asymmetric Reduction ◽  
Practical Synthesis ◽  
Optically Pure

scholarly journals ω-Amino Acid:Pyruvate Transaminase from Alcaligenes denitrificans Y2k-2: a New Catalyst for Kinetic Resolution of β-Amino Acids and Amines

2004 ◽  
Vol 70 (4) ◽  
pp. 2529-2534 ◽  
Author(s):  
Hyungdon Yun ◽  
Seongyop Lim ◽  
Byung-Kwan Cho ◽  
Byung-Gee Kim
Keyword(s):  
Amino Acids ◽  
Kinetic Resolution ◽  
Specific Activity ◽  
Expression System ◽  
Enantiomeric Excess ◽  
Selective Enrichment ◽  
Alcaligenes Denitrificans ◽  
Keto Acids ◽  
Optically Pure ◽  
High Stereoselectivity

ABSTRACT Alcaligenes denitrificans Y2k-2 was obtained by selective enrichment followed by screening from soil samples, which showed ω-amino acid:pyruvate transaminase activity, to kinetically resolve aliphatic β-amino acid, and the corresponding structural gene (aptA) was cloned. The gene was functionally expressed in Escherichia coli BL21 by using an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible pET expression system (9.6 U/mg), and the recombinant AptA was purified to show a specific activity of 77.2 U/mg for l-β-amino-n-butyric acid (l-β-ABA). The enzyme converts various β-amino acids and amines to the corresponding β-keto acids and ketones by using pyruvate as an amine acceptor. The apparent Km and V max for l-β-ABA were 56 mM and 500 U/mg, respectively, in the presence of 10 mM pyruvate. In the presence of 10 mM l-β-ABA, the apparent Km and V max for pyruvate were 11 mM and 370 U/mg, respectively. The enzyme exhibits high stereoselectivity (E > 80) in the kinetic resolution of 50 mM d,l-β-ABA, producing optically pure d-β-ABA (99% enantiomeric excess) with 53% conversion.

scholarly journals Chemoenzymatic Synthesis of Synthes as Precursors for Enantiopure Clenbuterol and Other β2 Agonists

Catalysts ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 516
Author(s):  
Fredrik Blindheim ◽  
Mari Hansen ◽  
Sigvart Evjen ◽  
Wei Zhu ◽  
Elisabeth Jacobsen
Keyword(s):  
Protein Synthesis ◽  
Nicotinamide Adenine Dinucleotide ◽  
Asymmetric Reduction ◽  
Enantiomeric Excess ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
The Body ◽  
Chemoenzymatic Synthesis ◽  
The World ◽  
Β2 Agonist ◽  
Β2 Agonists

Clenbuterol is a β2-agonist used in the veterinary treatment of asthma in several countries. The drug is listed on the World Antidoping Agency’s prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, pure enantiomers need to be separately studied. (R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor in dimethyl sulfoxide (DMSO). (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers.

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