821783-49-7

Upstream product

• 110508-08-2 Ethyl (2S,3S)-2,3-epoxybutanoate 
• 106-48-9 4-chloro-phenol 
• 110444-43-4 ethyl (2R,3S)-2-chloro-3-hydroxybutanoate 
• 119138-47-5 ethyl 2-(4-chlorophenoxy)-3-oxobutanoate 
• 609-15-4 ethyl 2-chloro-3-oxo-butyrate 

Relevant academic research and scientific papers

Stereoselective prostereogenic 3-oxo ester reduction mediated by a novel yeast alcohol dehydrogenase derived from Kluyveromyces marxianus CBS 6556

A yeast alcohol dehydrogenase (ADH) has been purified up to a purification factor value of 21,731-fold from Kluyveromyces marxianus CBS 6556. The purification procedure consisted of two chromatographic steps (DEAE-anion exchange and affinity chromatography). The optimal pH was 7, its optimal temperature was 40°C and its co-factor was NADPH. This novel ADH efficiently mediated the reduction of 3-oxo esters with a high degree of stereoselectivity, providing chiral alcohols having the (S) absolute configuration at the newly formed stereogenic centre by delivering the hydride from the re-face of the prochiral carbonyl compounds.

Reaction of caesium 4-chlorophenate and chlorohydrins from threonines: Synthesis of clofibrate analogues

Clofibrate is a well-known peroxisome proliferator-activated receptor-α (PPARα) agonist, used in the treatment of hyperlipaemias and atherosclerosis and to prevent heart failure. Herein, the preparation of the four enantiomerically pure stereoisomers of e

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

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.

Baker's yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3- oxoalkanoates intermediates for potential PPARα ligands

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.