Chin. J. Org. Chem. ›› 2008, Vol. 28 ›› Issue (09): 1584-1589. Previous Articles     Next Articles

Original Articles


王世珍; 吴坚平 ; 徐 刚 ; 杨立荣*   

  1. (浙江大学化学与生物工程学系 杭州 310027)
  • 收稿日期:2007-11-19 修回日期:2008-04-17 发布日期:2008-09-20
  • 通讯作者: 杨立荣

Resolution of Citalopram Intermediate by Enzyme-Catalyzed Enantioselective Transesterification in Organic Media

WANG, Shi-Zhen; WU, Jian-Ping; XU, Gang; YANG, Li-Rong*   

  1. (Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou 310027)
  • Received:2007-11-19 Revised:2008-04-17 Published:2008-09-20
  • Contact: YANG, Li-Rong

The lipase-catalyzed remote kinetic resolution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)- 1-hydroxy-1-butyl]-3-(hydroxymethyl)-benzonitrile (1), a useful intermediate of citalopram with a quater-nary chiral center, was studied. Through screening, the preferable system for the asymmetric reaction was: Candida antarctica lipase B (Novozym435) as a catalyst, acetonitrile as a solvent and vinyl acetate as an acyl donor. The influence of various parameters on the enzymatic resolution was studied. The optimal con-dition was as follows: temperature of 30 ℃, the molar ratio of diol 1 to vinyl acetate 1 to 5, 10 mg/mL li-pase, and 200 r/min rotation speed. Reaction curves of 180 and 60 mmol/L diol 1 concentrations ensured the high reaction rate and enantioselectivity. Reusability study ensured the operational stability of lipase over repeated cycles.

Key words: lipase, organic media, remote kinetics resolution, citalopram, transesterification