绿茶儿茶素的最新合成进展有机化学.pdfVIP

2007 年第 27 卷 有 机 化 学 Vol. 27, 2007 第 12 期, 1509～1515 Chinese Journal of Organic Chemistry No. 12, 1509～1515 ·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 (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) 摘要 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 A New Synthetic Method of Natural Product Trichostatin A ZHAO, Xia ZHANG, Shi-Lei*,a,b DUAN, Wen-Hu*,a,b 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) Abstract 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 proc- ess and the synthetic trichostatin A was a pure R enantiomer with more than 99% ee.