Preparation Of (R)-(-)-mandelic Acid Methyl Ester And(R)-(-)-mandelic Acid Ethyl Ester By Microbial Conversion

In this paper, High optical purity of (R)-(-)-mandelic acid methyl ester and (R)-(-)-mandelic acid ethyl ester were obtained by microbiological method, they are important intermediate of chiral drugs.Enantiopure alcohols are the key chiral building blocks for many important chiral pharmaceutical.(R)-(-)-mandelic acid methyl ester and (R)-(-)-mandelic acid ethyl ester are important enantiopure alcohols of chiral drugs. Microbio logical method was one of the most promising synthetic routes to produce enantiopure alcohols.Candida pseudotropicalis104was selected from strains kept in this laboratory. The enantiometric execss of (R)-(-)-mandelic acid methyl ester can achieve99.8%in water/chloroform two phase system. The optimum phase volume ratio was1:1. The shake speed was180r/min. temperature30℃,pH7.0.reaction time36h.But the conversion of (R)-(-)-mandelic acid methyl ester was only60.8%with Candida pseudotropicalis104as catalyst in water/chloroform two phase system. In order to improve the conversion of (R)-(-)-mandelic acid methyl ester, Saccharomyces cerevisiae zjut21was obtained by UV mutagenesis of Candida pseudotropicalis104. The biotransformation process was optimized and the optimum reduction conditions were as follows. Biomass of Saccharomyces cerevisiae zjut21was150g/L.Substrate concentration was0.13mol/L. Shaking speed was180r/min, temperature30℃,pH7.0,reaction time36h.Continuous reduction of (R)-(-)-mandelic acid methyl ester was studied to eliminate the substrate inhibition The results show that continuous reduction can enhance the conversion. When circulating pump rate get to40r/min,0.25mol/L of (R)-(-)-mandelic acid methyl estercanbe converted completely.The conversion and the enantiometric execss of (R)-(-)-mandelic acid ethyl ester can achieve100%by asymmetric reduction of benzoylformate ethyl with Saccharomyces cerevisiae zjut21as catalyst The bio transformation process was optimized and the optimum reduction conditions were as follows. Biomass of Saccharomyces cerevisiae zjut21was140g/L. Substrate concentration was0.11mol/L. Shaking speed was185r/min,temperature30℃,pH7.0,reaction time36h.Based on the preparation of (R)-(-)-mandelic acid methyl ester and (R)-(-)-mandelic acid ethyl ester,5L reaction tank of amplification experiments with Saccharomyces cerevisiae zjut21respectively.The results show that the amplification technology is feasibility. Also proved that the strain Saccharomyces cerevisiae zjut21was valueable for industrial application.