Growing and resting cells of several yeasts, which catalyze the hydride transfer to a carbonyl, were screened and used in conditions to find out the suitable methodology to prepare clofibrate analogues. Clofibrate is an antilipidemic drug. In particular, the bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate 1 was investigated to separately prepare the four possible stereoisomers of the ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate 2. Compound (2R,3S)-2 was prepared with ee = 97% and 73% yield in the presence of Kluyveromyces marxianus; (2S,3S)-2 preparation with ee > 99% in 9% and 33% yield was mediated by Saccharomyces cerevisiae CBS 7336 and Trigonopsis variabilis, respectively. Diastereomeric excess values of all the reactions investigated were up to > 99%. Furthermore, enantiomeric excesses of the bioconversions varied between 2% and > 99% using growing cells and, 12% and > 99% using resting cells. The absolute configuration of (2R,3S)-2 was established by X-ray analysis of the corresponding acid 3.

Diastereo- and enantioselective bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate clofibrate analogues by Kluyveromyces marxianus and other whole cell biocatalysts

BERTOLASI, Valerio
2004

Abstract

Growing and resting cells of several yeasts, which catalyze the hydride transfer to a carbonyl, were screened and used in conditions to find out the suitable methodology to prepare clofibrate analogues. Clofibrate is an antilipidemic drug. In particular, the bioreduction of ethyl 2-(4-chlorophenoxy)-3-oxobutanoate 1 was investigated to separately prepare the four possible stereoisomers of the ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate 2. Compound (2R,3S)-2 was prepared with ee = 97% and 73% yield in the presence of Kluyveromyces marxianus; (2S,3S)-2 preparation with ee > 99% in 9% and 33% yield was mediated by Saccharomyces cerevisiae CBS 7336 and Trigonopsis variabilis, respectively. Diastereomeric excess values of all the reactions investigated were up to > 99%. Furthermore, enantiomeric excesses of the bioconversions varied between 2% and > 99% using growing cells and, 12% and > 99% using resting cells. The absolute configuration of (2R,3S)-2 was established by X-ray analysis of the corresponding acid 3.
2004
Perrone, Mg; Santandrea, E; Scilimati, A; Syldatk, C; Tortorella, V; Capitelli, F; Bertolasi, Valerio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1198112
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