合成天然产物曲古抑菌素A的新方法  

A New Synthetic Method of Natural Product Trichostatin A

作　　者：赵曦[1] 张士磊[1] 段文虎[1] 

机构地区：[1]中国科学院上海生命科学研究院上海药物研究所,上海201203

出　　处：《有机化学》2007年第12期1509-1515,共7页Chinese Journal of Organic Chemistry

基　　金：中国科学院知识创新工程重要方向(No.06G8031014);国家863(No.2006AA020602)资助项目.

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%.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 ： syh =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.

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 

分 类 号：TQ465[化学工程—制药化工]