色谱

色谱 ›› 2015, Vol. 33 ›› Issue (6): 647-651.DOI: 10.3724/SP.J.1123.2015.01038

• 研究论文 • 上一篇    下一篇

Chiralpak AD和Chiralcel OD-H手性固定相拆分3α-酰氧基-6β-乙酰氧基莨菪烷类化合物

成斌1, 谢一凡1, 胡优敏2, 刘慧中3, 钮因尧1, 陆阳1   

  1. 1. 上海交通大学医学院药学系化学教研室, 上海 200025;
    2. 上海交通大学医学院实验教学中心功能学 实验室, 上海 200025;
    3. 上海交通大学医学院实验教学中心化学生物学实验室, 上海 200025
  • 收稿日期:2015-01-27 发布日期:2015-05-26
  • 通讯作者: 钮因尧
  • 基金资助:

    上海市卫生计生委科研课题(201440575);上海交通大学医学院科技基金项目(201406).

Enantioseparation of 3α-acyloxy-6β-acetoxyltropane compounds with Chiralpak AD and Chiralcel OD-H chiral stationary phases

CHENG Bin1, XIE Yifan1, HU Youmin2, LIU Huizhong3, NIU Yinyao1, LU Yang1   

  1. 1. Division of Chemistry, Department of Pharmacy, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China;
    2. Functional Training Laboratory, Experiment-teaching Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China;
    3. Chemicobiological Laboratory, Experiment-teaching Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
  • Received:2015-01-27 Published:2015-05-26

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摘要：

采用高效液相色谱法,以不同配比的正己烷-异丙醇为流动相,在正相色谱条件下,考察了6个3α-酰氧基-6β-乙酰氧基莨菪烷对映体在淀粉型手性固定相Chiralpak AD、纤维素型手性固定相Chiralcel OD-H上的分离情况,以建立该类化合物的手性拆分方法。结果表明,在Chiralpak AD手性柱上,对映体6实现完全分离,而对映体1完全不能分离;在Chiralcel OD-H柱上,对映体1、4、3分别实现完全分离、基线分离和基本分离,对映体6只能实现部分分离;对映体5在两种手性柱上都完全不能被分离。说明固定相手性空腔的结构对化合物的拆分结果影响很大。研究发现,C-3α 位取代基团的空间位阻效应主导手性固定相对对映体的选择性识别作用,而化合物与固定相之间的分子间作用力对手性拆分也产生重要影响。研究结果为其他莨菪烷类化合物的手性拆分提供了参考。

关键词: 对映体, 高效液相色谱, 莨菪烷, 手性拆分

Abstract:

Six 3α-acyloxy-6β-acetoxyltropane compounds were enantioseparated by high performance liquid chromatography with amylose-based chiral stationary phase Chiralpak AD and cellulose-based chiral stationary phase Chiralcel OD-H in the normal phase mode, using various mixtures of n-hexane-isopropanol as mobile phases. The enantiomers 6 were completely separated on a Chiralpak AD column. While the enantiomers 1, 4 and 3 got complete, baseline and basic separation respectively on a Chiralcel OD-H column. However, the enantiomers 6 were partially separated on the Chiralcel OD-H column and enantiomers 1 could not be separated on the Chiralpak AD column. This indicated that the cave structure of chiral stationary phase exerted great effect on the resolutions. The enantiomers 5 could not be separated on both of the chiral stationary phases. The main possible mechanism of chiral resolution involves in spatial adaptability and molecular interactions between chiral stationary phases and compounds. The substituents in C-3α position of 3α-acyloxy-6β-acetoxyltropane compounds play an important role in spatial adaptability. And it was suggested that the steric hindrance effect of the substituent in C-3α position was the key factor of determining the selective recognition of chiral stationary phase to the enantiomers of 3α-acyloxy-6β-acetoxyltropane compounds. Besides, the molecular interaction, such as π-π interaction, also exerts great influence to the chiral resolution. This study provides a reference for the enantioseparation of many other tropane derivatives.

Key words: chiral resolution, enantiomer, high performance liquid chromatography (HPLC), tropane

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