上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (4): 406-.doi: 10.3969/j.issn.1674-8115.2011.04.005

• 论著（基础研究） • 上一篇    下一篇

山莨菪碱4个异构体的分离及其抗胆碱活性比较

孙 凯, 谢一凡, 崔永耀, 陈红专, 陆 阳, 杨丽敏   

  1. 上海交通大学 医学院药学系, 上海 200025
  • 出版日期:2011-04-28 发布日期:2011-04-28
  • 通讯作者: 杨丽敏, 电子信箱: hxyanglm@shsmu.edu.cn。
  • 作者简介:孙 凯（1984—）, 女, 硕士生；电子信箱: wwsunkai@163.com。
  • 基金资助:

    上海市教委基金（06BZ009）和上海市科委基金（06DZ19001）

Separation of four stereoisomers of anisodamine and comparison of their anticholinergic activity

SUN Kai, XIE Yi-fan, CUI Yong-yao, CHEN Hong-zhuan, LU Yang, YANG Li-min   

  1. Department of Pharmacy, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2011-04-28 Published:2011-04-28
  • Supported by:

    Shanghai Education Committee Foundation, 06BZ009；Shanghai Science and Technology Committee Foundation, 06DZ19001

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摘要：

目的 探讨山莨菪碱立体异构与生物活性的关系。方法 采用MDS-5型反相制备色谱柱直接分离山莨菪碱得到外消旋体Ⅰ和Ⅱ，用手性半制备高效液相色谱柱分离Ⅰ和Ⅱ得到山莨菪碱的4个单一异构体，通过抗卡巴胆碱致大鼠气管收缩效应实验考察4个异构体的抗胆碱活性。结果 由1H NMR谱和比旋光度值确定了山莨菪碱4个异构体的绝对构型，不同的立体构型对卡巴胆碱诱导的大鼠气管平滑肌收缩表现出不同程度的抑制作用，效应强度为（6S, 2-S）>（6S, 2-R）>（6R, 2-S）>（6R, 2-R）。结论 山莨菪碱莨菪烷母核上的S构型在抗胆碱活性上发挥更重要的作用。

关键词: 山莨菪碱, 立体异构体, 气管平滑肌

Abstract:

Objective To investigate the relationship between stereoisomerism and pharmacological activity of anisodamine. Methods Two racemates of anisodamine （Ⅰand Ⅱ） were separated from synthetic anisodamine using MDS-5 column, and four stereoisomers of anisodamine were separated fromⅠ and Ⅱby high performance liquid chromatography using CHIRALPAK AD-H. The anticholinergic activities of four stereoisomers were compared by their inhibitory effects on carbachol-induced contractions of isolated rat tracheal smooth muscle. Results The absolute configurations of four stereoisomers were assigned using 1H NMR chemical shifts and specific rotation values. The difference of anticholinergic activities was observed among the four isomers of anisodamine. The order of potency was （6S, 2-S）＞（6S, 2-R）＞（6R, 2-S）＞（6R, 2-R）. Conclusion (S) configuration at the tropane ring plays more important role in the anticholinergic activity of anisodamine.

Key words: anisodamine, stereoisomers, tracheal smooth muscle