度洛西汀手性中间体的生物合成  

Biosynthesis of Chiral Intermediate for Duloxetine

作　　者：陈宇涵 鄢定玉 阳小姣 钟国寿 CHEN Yuhan;YAN Dingyu;YANG Xiaojiao;ZHONG Guoshou(Chengdu Longquanyi Second People's Hospital,Chengdu 610100;Chongqing Medical University,Chongqing 400016;Chengdu Maternity and Child Health Care Hospital of Longquanyi District,Chengdu 610199)

机构地区：[1]成都市龙泉驿区第二人民医院,四川成都610100 [2]重庆医科大学,重庆400016 [3]成都市龙泉驿区妇幼保健院,四川成都610199

出　　处：《中国医药工业杂志》2021年第11期1476-1479,1486,共5页Chinese Journal of Pharmaceuticals

摘　　要：本研究报道了2种运用重组工程菌,以3-二甲胺基-1-(噻吩-2-基)-1-丙酮(2)为底物,建立生物合成重度抑郁治疗药度洛西汀的重要手性中间体(S)-3-二甲胺基-1-(噻吩-2-基)-1-丙醇(1)的高效、低成本、绿色新方法。优化后4 h底物转化率达到99%以上,产物收率高达85%,且ee值大于99%。该方法利用酶偶联和底物偶联2种方法实现了辅酶循环,无需添加外源性辅酶,可显著降低生产成本,为重度抑郁治疗药度洛西汀关键中间体的规模化生产提供了技术支持。In this paper,two efficient,low cost,eco-friendly solutions of biosynthesis of duloxetine key intermediate(S)-3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol(1)was reported by using two recombinant strains as catalyst,3-(dimethylamino)-1-(thiophen-2-yl)propan-1-one(2)as substrate.After optimization of reactions,99%of substrate conversion was reached in 4 h with 85%of yield and ee 99%.Enzyme coupling and substrate coupling were used to realize the coenzyme cycle without adding exogenous coenzymes,which significantly reduced production costs.These solutions reported offered technical support for industrial production of the key intermediate of duloxetine for treatment of severe depression.

关 键 词：生物合成 (S)-3-二甲胺基-1-(噻吩-2-基)-1-丙醇 度洛西汀 中间体 不对称合成 辅酶循环 

分 类 号：O626.12[理学—有机化学]