849704-24-1Relevant articles and documents
Baker's yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3- oxoalkanoates intermediates for potential PPARα ligands
Perrone, Maria Grazia,Santandrea, Ernesto,Scilimati, Antonio,Tortorella, Vincenzo,Capitelli, Francesco,Bertolasi, Valerio
, p. 3501 - 3510 (2004)
Several 2-(4-chlorophenoxy)-3-oxoesters were prepared in fair to good yields and then reduced in the presence of baker's yeast to the corresponding alcohols having de's up to 92% and ee's >99%. The absolute configuration of nearly enantiomerically pure ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate was assigned by both comparison of the sign of the specific rotation and HPLC retention times of authentic samples prepared from threonines. Reduction of ethyl 2-(4-chlorophenoxy)-3-oxo-4-phenylbutanoate afforded only enantiomerically pure ethyl (2R,3S)-2-(4-chlorophenoxy)-3-hydroxy-4-phenylbutanoate (out of the four possible stereoisomers), whose absolute configuration was established by single crystal X-ray analysis. Furthermore, reduction of ethyl 2-methyl-2-(4-chlorophenoxy)-3-hydroxybutanoate with a quaternary stereogenic carbon (C2) gave both of the two expected diastereoisomers with ee = 95% and 96%. Insight into the mechanism of baker's yeast-mediated reduction of prochiral ketoesters is also reported.
Diastereo- and enantioselective bioreduction of ethyl 2-(4-chlorophenoxy)- 3-oxobutanoate clofibrate analogues by Kluyveromyces marxianus and other whole cell biocatalysts
Perrone, Maria Grazia,Santandrea, Ernesto,Scilimati, Antonio,Syldatk, Christoph,Tortorella, Vincenzo,Capitelli, Francesco,Bertolasi, Valerio
, p. 3511 - 3517 (2007/10/03)
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.