酵母菌DM10不对称合成(R)-(-)邻氯扁桃酸甲酯

目的合成(S)-氯吡咯雷的关键中间体——(R)-(-)邻氯扁桃酸甲酯,并建立了优化的还原条件。方法以邻氯苯乙酮酸甲酯为底物,利用酵母菌DM10的醇脱氢酶及其辅酶合成(R)-(-)邻氯扁桃酸甲酯,并考察了底物质量浓度、初始pH、转化温度和反应时间对不对称还原的影响。结果和结论获得优化的还原条件:接种量体积分数为10%,初始pH值为6.5,底物质量浓度为1 g.L-1,温度为30℃,转化36 h,转化率为98.75%,产率为82.25%,对映体过量值为95.1%。

Asymmetric synthesis of methyl (R)-o-chloromandelate by Saccharomyces cerevisiae DM10

Objective To prepare methyl (R)-o-chloromandelate (key intermediate for (S)-clopidogrel ) and establish the optimal conditions. Methods Methyl 2-chlorobenzoylformate was transformed to methyl (R)-o-chloromandelate by enzyme system of alcohol dehydrogenase and coenzyme in Saccharomyces cerevisiae DM10. Effects of some factors on the asymmetric reduction, including substrate concentrations, initial pH, temperature and reaction time, were studied. Results and conclusion The optimal reaction conditions was obtained:10% inoculums of the conversion solution, substrate concentration was 1 g·L^-1,the initial pH value was 6.5,temperature was set at 30 °C,the reaction was maintained for 36 h,the conversion was 98.75% with the yield of 82.25% and enantiomeric excess of 95.1%.