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有机化学
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有机化学 ›› 2007, Vol. 27 ›› Issue (12): 1509-1515. 上一篇    下一篇

研究论文

合成天然产物曲古抑菌素A的新方法

赵曦a，张士磊*,a,b，段文虎*,a,b   

  1. (a中国科学院上海生命科学研究院上海药物研究所 上海 201203)
    (b华东理工大学药学院药物科学系 上海 200237)
  • 收稿日期:2007-03-30 修回日期:2007-06-06 发布日期:2007-12-04
  • 通讯作者: 张士磊,段文虎

A New Synthetic Method of Natural Product Trichostatin A

ZHAO Xia, ZHANG Shi-Lei*,a,b, DUAN Wen-Hu*,a,b   

  1. (a Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203)
    (b Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology,
    Shanghai 200237)
  • Received:2007-03-30 Revised:2007-06-06 Published:2007-12-04
  • Contact: ZHANG Shi-Lei, DUAN Wen-Hu

被引次数

1

报道了一条组蛋白去乙酰化酶抑制剂曲古抑菌素A的有效合成路线. 通过L-脯氨酸催化对硝基苯甲醛与丙醛的羟醛缩合反应, 高立体选择性地构建了目标分子的手性中心, 羟醛缩合产物的ee值大于99%, anti∶syn＝16∶1. 随后的合成过程中无消旋化现象, 合成的曲古抑菌素A是单一R型异构体, ee值大于99%.

关键词: 曲古抑菌素A, 组蛋白去乙酰酶抑制剂, L-脯氨酸, 合成

An efficient synthesis of trichostatin A, a potent histone deacetylase inhibitor, was reported. The key point in this new approach lied in the highly stereocontrolled establishment of its chiral center using L-proline-catalyzed aldol reaction between p-nitrobenzaldehyde and propaldehyde. The aldol product was obtained with ＞99% ee and high de (anti∶syn＝16∶1). No racemization was found in the following process and the synthetic trichostatin A was a pure R enantiomer with more than 99% ee.

Key words: histone deacetylase inhibitor, L-proline, synthesis, trichostatin A