Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic resolution and stereoinversion of quaternary stereogenic center

CORC > 厦门大学 > 化学化工－已发表论文

	Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic resolution and stereoinversion of quaternary stereogenic center
	Wang, Shi-Zhen ; Wu, Jian-Ping ; Xu, Gang ; Yang, Li-Rong ; Wang SZ(王世珍)
刊名	http://dx.doi.org/10.1007/s00449-012-0855-5
	2013
关键词	KINETIC RESOLUTION TERTIARY ALCOHOLS CONFIGURATION MITSUNOBU INVERSION
英文摘要	National Natural Science Foundation of China [20936002]; Key Project of Chinese National Programs for Fundamental Research and Development [2011CB710800]; Hi-Tech Research and Development Program of China [2011AA02A209]; A chemo-enzymatic synthesis method of S-citalopram was developed to overcome the disadvantage of relatively low selectivity of enzyme towards tertiary alcohols. The combination of kinetic resolution, cyclic resolution and stereoinversion synthesis was successfully applied in the asymmetric synthesis of the S-citalopram. Using the kinetic model to predict the cyclic resolution, R-diol with high ee value was obtained by controlling the conversion rate. Subsequently, the unwanted R-diol was inverted to S-citalopram by stereoinversion of chiral quaternary center with 98.0 % yield and ee value of 91.0 %. Based on dynamic simulation and experiments, the kinetic resolution was scaled up from 10 mL to 1 L and 14 L, gradually. There was no significant scale-up effect and the dynamic simulation result fitted the experimental data well, with an error of 12.5 and 14.0 %, respectively. This chemo-enzymatic synthesis route is a promising model system for the production of pharmaceuticals with the chiral tertiary alcohols intermediate.
语种	英语
出版者	SPRINGER
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/88958]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Wang, Shi-Zhen,Wu, Jian-Ping,Xu, Gang,et al. Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic resolution and stereoinversion of quaternary stereogenic center[J]. http://dx.doi.org/10.1007/s00449-012-0855-5,2013.
APA	Wang, Shi-Zhen,Wu, Jian-Ping,Xu, Gang,Yang, Li-Rong,&王世珍.(2013).Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic resolution and stereoinversion of quaternary stereogenic center.http://dx.doi.org/10.1007/s00449-012-0855-5.
MLA	Wang, Shi-Zhen,et al."Chemo-enzymatic asymmetric synthesis of S-citalopram by lipase-catalyzed cyclic resolution and stereoinversion of quaternary stereogenic center".http://dx.doi.org/10.1007/s00449-012-0855-5 (2013).