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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (08): 1185-1191. 上一篇    下一篇

研究论文

胆碱酯酶抑制剂(S)-卡巴拉汀及其类似物的不对称合成与活性研究

徐刚，文富华，买小胖，孙平华，黄美燕，陈卫民   

  1. (暨南大学药学院 广州 510632)
  • 收稿日期:2009-10-06 修回日期:2009-12-23 发布日期:2010-03-16
  • 通讯作者: 陈卫民 E-mail:twmchen@jnu.edu.cn

Asymmetric Synthesis and Biological Evaluation of Cholinesterase Inhibitor Rivastigmine and Analogues Thereof

XU Gang, WEN Fu-Hua, MAI Xiao-pang, SUN Ping-Hua, HUANG Mei-Yan, CHEN Wei-Min   

  1. (Medical College, Jinan University, Guangzhou 510632)
  • Received:2009-10-06 Revised:2009-12-23 Published:2010-03-16
  • Contact: Wei-Min CHEN E-mail:twmchen@jnu.edu.cn

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以对羟基苯甲醛或间羟基苯甲醛为原料, 用(R)或(S)-叔丁基亚磺酰胺为手性引发剂, 设计合成了(S)-卡巴拉汀及其12个未见文献报道的类似物, 其结构通过IR, 1H NMR, 13C NMR和HR MS确证. 以Ellman法进行化合物的活性测试, 结果表明合成的化合物都有较好的对乙酰胆碱酯酶以及丁酰胆碱酯酶抑制活性, 部分化合物的活性甚至比卡巴拉汀(rivastigmine)更好.

关键词: 不对称合成, 胆碱酯酶抑制剂, 卡巴拉汀, 类似物

(S)-Rivastigmine and twelve chiral analogues were synthesized starting from p-hydroxybenz- aldehyde or m-hydroxybenzaldehyde via (R)- or (S)-tert-butanesulfinylimines as a chiral initiator, and characterized by IR, 1H NMR, 13C NMR and HR-MS techniques. Ellman’s method was applied to evaluate their bio-activities. Results showed that these compounds exhibited potent inhibitory activities of acetylcholinesterase and butyrylcholinesterase, some of them even superior to rivastigmine.

Key words: asymmetric synthesis, cholinesterase inhibitor, rivastigmine, analogue

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