酶法动态动力学拆分制备R-(-)-乙酰基邻氯扁桃酸

R-(-)-acetyl-o-mandelic acid preparation via enzymatic dynamic kinetic resolution

采用假单胞菌脂肪酶Pseudomonas sp.ECU1011催化乙酰基邻氯扁桃酸进行不对称水解,利用突变后的扁桃酸消旋酶(V29I)对拆分后的产物S-(-)-邻氯扁桃酸进行消旋,消旋后的邻氯扁桃酸经过酰化重新被利用到水解反应中,实现了酶法动态动力学拆分制备R-(-)-乙酰基邻氯扁桃酸。通过对拆分反应、拆分混合物的分离回收以及消旋反应的工艺优化,最终获得光学纯度ee>99.9%的R-(-)-乙酰基邻氯扁桃酸,其收率达80%。本研究建立的R-(-)-乙酰基邻氯扁桃酸的动态动力学拆分工艺,对其工业化应用具有重要的指导意义。

In this study,asymmetric hydrolysis of acetyl chloromandelic acid was catalyzed by Pseudomonas sp. ECU1011,and the S-（-）-chloromandelic acid in the resolution mixture was then racemerized using the mutated mandelate racemase and fed back into the hydrolysis reaction after acylation , realizing enzymatic dynamic kinetic resolution for preparation of R-（-）-acetyl chloromandelic acid. Firstly,the conditions for enzymatic resolution,separation of resolution mixture, and enzymatic racemization were optimized. Subsequently,dynamic kinetic resolution of acetyl chloromandelic acid was conducted under the optimal conditions,obtaining optically pure R-（-）-acetyl chloromandelic acid with final yield of 80%. The conditions for enzymatic resolution,chloromandelic acid recycling and racemization were optimized in this study,leading to preliminary establishment of the dynamic kinetic resolution process for R-（-）-acetyl chloromandelic acid preparation,with guiding significance for future industrial applications.