关键词: R-(-)-扁桃酸, 不对称还原, 立体选择性, 手性合成

Abstract: R-(-)-mandelic acid is an important multifunctional pharmaceutical intermediate in the preparation of chiral drugs. A sp. strain by1 from 18 strains of Saccharomyces cerevisiae, Lactoballius, Streptococcus faecalis, Candida albicans had been screened for transforming phenylglyoxilic acid to R-(-)-mandelic acid. In this article, to study further the asymmetric bioreduction of phenylglyoxylic acid to mandelic acid by Saccharomyces cerevisiae sp. strain by1, the effect of biochemical factors on the conversion efficiency of substrate phenylglyoxylic acid and enantiomeric excess of product R-mandelic acid were investigated in detail. For some conditions tested in our experiments, the sp. strain by1 showed very high enantioselectivity toward the bioreduction of the substrates. The enantiomeric excess value of desired product R-(-)-mandelic acid reached up to 94.0%. Whereas, the conversion of substrate and the yield of product mandelic acid were influenced evidently by the environmental factors. The substrate conversion and the yield of product decreased sharply with the increase of initial substrate concentration up to 20 mmol/L. The high concentration of substrates inhibits strongly the activity of redoxase of yeast cells. Under the optimal conditions: pH 6.5, 32oC, initial concentration 15 mmol/L, absolute anaerobic cultivation 28 h, the substrate conversion rate of 97.0% and yield of product mandelic acid of 96.1% and enantiomeric excess value of R-(-)-mandelic acid of 95.1% could been obtained. This research paces the way for economic preparation of chiral R-(-)-mandelic acid.

Key words: R-(-)-mandelic acid, asymmetric reduction, enantioselectivity, chiral synthesis