对映体纯的不对称顺式-2,5-二取代吡咯烷的简便合成路线。

Facile synthetic route to enantiopure unsymmetric cis-2,5-disubstituted pyrrolidines.

作者信息

Wang Ping-An, Xu Zheng-Shuang, Chen Chun-Feng, Gao Xu-Guang, Sun Xiao-Li, Zhang Sheng-Yong

机构信息

Department of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Chirality. 2007 Jul;19(7):581-8. doi: 10.1002/chir.20424.

DOI:10.1002/chir.20424

PMID:17508396

Abstract

The (+/-)-cis-5-arylcarbamoyl-2-ethoxycarbonylpyrrolidines 6a-g were firstly synthesized in 53-64% yields by using meso-diethyl-2,5-dibromoadipate 3 and (S)-(-)-1-phenylethylamine in three steps. The diastereomeric mixture (S;2S,5R)-(-)-7 and (S;2R,5S)-(+)-8 were prepared by the Grignard reaction and separated by a flash column chromatography in 29 and 52% yields. The absolute configurations of (+)-8 was confirmed by X-ray crystallographic analysis and the enantiopure pyrrolidines (2S,5R)-(-)-9/(2R,5S)-(+)-9 and (2S,5R)-(-)-10/(2R,5S)-(+)-10 were obtained in good yields.

摘要

首先，使用内消旋二乙基-2,5-二溴己二酸酯3和(S)-(-)-1-苯乙胺，通过三步反应以53 - 64%的产率合成了(±)-顺式-5-芳基氨基甲酰基-2-乙氧羰基吡咯烷6a - g。通过格氏反应制备了非对映异构体混合物(S;2S,5R)-(-)-7和(S;2R,5S)-(+)-8，并通过快速柱色谱法分离，产率分别为29%和52%。通过X射线晶体学分析确定了(+)-8的绝对构型，并以良好的产率获得了对映体纯的吡咯烷(2S,5R)-(-)-9/(2R,5S)-(+)-9和(2S,5R)-(-)-10/(2R,5S)-(+)-10。