Asymmetric Carbonyl Reductions with Microbial Ketoreductases (original) (raw)
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Microorganisms' mediated reduction of �-ketoesters
Lactobacillus were screened for their ability to perform the reduction of γ γ γ γ-chloro-β-ketobutyric acid ethyl ester to γ γ γ γ-chloro-β-hydroxybutyric acid ethyl ester. The optimal conditions for both stages of the bioprocess were established. Both stereoisomers of γ γ γ γ-chloro-β-hydroxybutyric acid ethyl ester were obtained in different biotransformation conditions. While in aqueous medium the S isomer was obtained, in organic media the product had predominantly the R configuration.
Organic Letters, 2005
The biocatalytic reduction of r-alkyl-1,3-diketones and r-alkyl-keto esters employing 1 of 20 different isolated NADPH-dependent ketoreductases proved to be a highly efficient method for the preparation of optically pure keto alcohols or hydroxy esters. Optically active R-alkyl-hydroxy ketones and R-alkyl-hydroxy esters are important compounds in asymmetric organic synthesis, where they are used as building blocks for synthesis of polyketides, statins, protease inhibitors, and other important pharmaceuticals. 1 They are of relatively small molecular weight, bear chirality at two stereogenic centers, and contain at least two reactive functionalities (an alcohol,
Selection of microbial biocatalysts for the reduction of cyclic and heterocyclic ketones
Process Biochemistry, 2017
Biocatalysts for prochiral heterocyclic ketone reduction were selected by screening E. chrysanthemi and M. racemosus almost quantitatively reduced cyclododecanone. E. carotovora produced (S)-N-Boc-3-pyrrolidinol with 87% yield and 99%ee. X. fragariae produced (S)-1-phenylethanol with 100% yield and 79%ee. G. candidum produced (R)-1-phenylethanol with 55% yield and 93%ee.
International Letters of Natural Sciences, 2013
Microbial conversions are gaining importance in the synthesis of important drug metabolites and their intermediates as they are good alternative to chemical synthesis since they are enantio-selective and regio-selective and even can be carried out at ambient temperature and atmospheric pressure. Till date, biocatalytic reduction of acetophenone and its derivatives has been widely reported. In the present study, we have made an attempt to carry out the microbial bioreduction of o-hydroxyacetophenone by screening some of the selected microorganisms which were obtained from culture collection centre as well as those which are isolated in our Microbiology lab. The selected microorganisms include Aspergillus ochraceous, Aspergillus flavus, Aspergillus tubingenesis, Aspergillus niger, Rhizopus stolanifer MTCC 162, Rhizopus stolanifer MTCC 2591 and Baker’s yeast.Among the seven microorganisms screened for the bioreduction of o-hydroxyacetophenone, Baker’s yeast and Aspergillus tubingenesis...
Applied microbiology and biotechnology, 2014
Enzyme-catalyzed enantioselective reductions of ketones and keto esters have become popular for the production of homochiral building blocks which are valuable synthons for the preparation of biologically active compounds at industrial scale. Among many kinds of biocatalysts, dehydrogenases/reductases from various microorganisms have been used to prepare optically pure enantiomers from carbonyl compounds. (S)-1-phenylethanol dehydrogenase (PEDH) was found in the denitrifying bacterium Aromatoleum aromaticum (strain EbN1) and belongs to the short-chain dehydrogenase/reductase family. It catalyzes the stereospecific oxidation of (S)-1-phenylethanol to acetophenone during anaerobic ethylbenzene mineralization, but also the reverse reaction, i.e., NADH-dependent enantioselective reduction of acetophenone to (S)-1-phenylethanol. In this work, we present the application of PEDH for asymmetric reduction of 42 prochiral ketones and 11 β-keto esters to enantiopure secondary alcohols. The hig...
Tetrahedron, 2006
The substrate selectivity and stereoselectivity of a series of ketoreductases were evaluated toward the reduction of two sets of b-ketoesters. Both the structural variety at b-position and the substituent at a-position greatly affected the activity and stereoselectivity of these ketoreductases. For the first set of b-ketoesters, at least one ketoreductase was found that catalyzed the formation of either (D) or (L) enantiomer of b-hydroxyesters from each substrate with high optical purity, with the only exception of ethyl (D)-3-hydroxy-3-phenylpropionate. For the second set of b-ketoesters with a-substituents, the situation is more complex. More commonly, a ketoreductase was found that formed one of the four diastereomers in optically pure form, with only a few cases in which enzymes could be found that formed two or more of the diastereomers in high optical purity. The continued development of new, more diverse ketoreductases will create the capability to produce a wider range of single diastereomers of 2-substituted-3-hydroxy acids and their derivatives.
Microorganisms' mediated reduction of &# 946-ketoesters
African Journal of …, 2010
African Journal of Biotechnology Vol. 7 (20), pp. 3515-3520, 20 October, 2008 Available online at http://www.academicjournals.org/AJB ISSN 16845315 © 2008 Academic Journals ... O. Popa1*, Narcisa Babeanu1, A. Vamanu1, E. Vamanu1 and Diana Barbulescu2
Tetrahedron: Asymmetry, 2009
A set of five fungal species, Botrytis cinerea, Trichoderma viride and Eutypa lata, and the endophytic fungi Colletotrichum crassipes and Xylaria sp., was used in screening for microbial biocatalysts to detect monooxygenase and alcohol dehydrogenase activities (for the stereoselective reduction of carbonyl compounds). 4-Ethylcyclohexanone and acetophenone were biotransformed by the fungal set. The main reaction pathways involved reduction and hydroxylations at several positions including tertiary carbons. B. cinerea was very effective in the bioreduction of both substrates leading to the chiral alcohol (S)-1phenylethanol in up to 90% enantiomeric excess, and the cis-trans ratio for 4-ethylcyclohexanol was 0:100. trans-4-Ethyl-1-(1S-hydroxyethyl)cyclohexanol, obtained from biotransformation by means of an acyloin-type reaction, is reported here for the first time. The absolute configurations of the compounds trans-4-ethyl-1-(1S-hydroxyethyl)cyclohexanol and 4-(1S-and 4-(1R-hydroxyethyl)cyclohexanone were determined by NMR analysis of the corresponding Mosher's esters.
Chemical Papers, 2020
Chiral heterocyclic secondary alcohols have received much attention due to their widespread use in pharmaceutical intermediates. In this study, Lactobacillus kefiri P2 biocatalysts isolated from traditional dairy products, were used to catalyze the asymmetric reduction of prochiral ketones to chiral secondary alcohols. Secondary chiral carbinols were obtained by asymmetric bioreduction of different prochiral substrates with results up to > 99% enantiomeric excess (ee). (R)-1-(benzofuran-2-yl)ethanol 5a, which can be used in the synthesis of pharmaceuticals such as bufuralols potent nonselective β-blockers antagonists, Amiodarone (cardiac anti-arrhythmic), and Benziodarone (coronary vasodilator), was produced in gram-scale, high yield and enantiomerically pure form using L. kefiri P2 biocatalysts. The gram-scale production was carried out, and 9.70 g of (R)-5a in enantiomerically pure form was obtained in 96% yield. Also, production of (R)-5a in terms of yield and gram scale through catalytic asymmetric reduction using the biocatalyst was the highest report so far. This is a cost-effective, clean and eco-friendly process for the preparation of chiral secondary alcohols compared to chemical processes. From an environmental and economic perspective, this biocatalytic method has great application potential, making it a green and sustainable way of synthesis.