双相体系中一种诱变株细胞催化制备(S)-奥美拉唑  

Preparation of(S)-Omeprazole by Biological Oxidation of Mutagenic Strains in Biphasic System

作　　者：王志勇 李德鹏 王繁业[1] WANG Zhiyong;LI Depeng;WANG Fanye(School of Chemical Engineering,Qingdao University of Science and Technology,Qingdao 266042,China)

机构地区：[1]青岛科技大学化工学院,山东青岛266042

出　　处：《青岛大学学报（工程技术版）》2020年第4期82-88,共7页Journal of Qingdao University(Engineering & Technology Edition)

基　　金：国家自然科学基金资助项目(21546004,21576145);山东省重点研发计划资助项目(2019GSF107027,2019GNC106028,2019GSF107033)。

摘　　要：针对传统方法制备(S)-奥美拉唑过程中存在的催化剂活性弱及底物浓度过低等问题,本文以氯仿-水双相体系为反应介质,采用R.rhodochrous诱变株细胞催化奥美拉唑硫醚的生物氧化制备(S)-奥美拉唑。使得底物及细胞浓度分别达到180 mmol/L和100 g/L,且得到较高的产率(99.29%)和对映体过量百分率(enantiomeric excess,ee%)。同时,采用响应面法(response surface methodology,RSM)优化反应条件,建立了(S)-奥美拉唑收率的二次多项式模型,该模型的相关系数(correlation coefficient,R 2)达到0.9990。研究结果表明,R.rhodochrous诱变株细胞表现出高对映选择性,催化活性以及底物和产物耐受性,可以用于高效制备手性亚砜。该研究对提高(S)-奥美拉唑单位体积产率及降低生产成本具有重要意义。Aiming at the problems of weak catalyst activity and low substrate concentration in the process of preparing(S)-omeprazole by traditional methods,this paper uses the chloroform-water two-phase system as the reaction medium and uses the R.rhodochrous mutant strain Cells catalyze the biological oxidation of omeprazole sulfide to prepare(S)-omeprazole.The substrate and cell concentration reached 180 mmol/L and 100 g/L,respectively,and a higher yield(99.29%)and enantiomeric excess(ee%)were obtained.Response surface methodology(RSM)was used to optimize the reaction conditions,and a quadratic polynomial model of(S)-omeprazole yield was established.The correlation coefficient(R 2)of the model reached 0.9990.The results of the study showed that R.rhodochrous mutagen strain cells exhibited high enantioselectivity,catalytic activity,substrate and product tolerance,and could be used to efficiently prepare chiral sulfoxides.This research is of great significance for increasing the yield per unit volume of(S)-omeprazole and reducing production costs.

关 键 词：生物氧化 氯仿-水双相系统 (S)-奥美拉唑 静息细胞 响应面法 

分 类 号：TQ463[化学工程—制药化工]