生物催化不对称还原制备(R)-2-羟基-4-苯基丁酸

以克隆表达的乳酸脱氢酶(D-LDH)为催化剂来还原前手性化合物2-羰基-4-苯基丁酸(OPBA),制备重要的手性中间体(R)-2-羟基-4-苯基丁酸(R-HPBA)。通过考察影响反应的各因素,确定了反应pH、初始底物浓度,酶加量及NAD+加量等参数。最后,以分批补料的方式进行产物制备,4 h内即可完全转化100 mmol/L底物。经验证,所得产物的构型完全正确,且e.e值>99.9%。

Preparation of (R)-2-Hydroxy-4-phenyl-butyric Acid by Biocatalytic Asymmetric Reduction

The important chiral intermediate(R)-2-hydroxy-4-phenyl butyric acid(R-HPBA)was prepared from prochiral compound,using lactate dehydrogenase(D-LDH)obtained by cloning and expression as the biocatalyst.The affecting factors such as pH,initial substrate concentration,enzyme loading,and NAD+ amount were investigated.Finally,the product was prepared from 100 mmol/L substrate in 4 h by a fed-batch process.The configuration of the target product obtained therein was confirmed,and the e.e > 99.9%.