Liu Zhi-Yu, Chen Ze-Cheng, Yu Cheng-Zhi, Wang Rui-Fang, Zhang Ru-Zhou, Huang Chu-Sheng, Yan Zheng, Cao De-Rong, Sun Jian-Bo, Li Gang
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, China.
Chemistry. 2002 Aug 16;8(16):3747-56. doi: 10.1002/1521-3765(20020816)8:16<3747::AID-CHEM3747>3.0.CO;2-A.
The total synthesis of epothilone A is described by the coupling four segments 4-7 a. Three of the segments, 4, 5 and 7 a, have only one chiral center; all other chiral centers were introduced by simple asymmetric catalytic reactions. The key steps are the ring opening of epoxide 5 with acetylide 8 for the construction of the C12-C13 cis double bond and a practical hydrolytic kinetic resolution (HKR) developed by Jacobsen group for the introduction the chiral center at C3. Especially, the stereospecific epoxidation of 3-O-PMB epothilone C 3 b through long-range effect of 3-O-PMB protecting group gave high yields of the C12-C13 alpha-epoxide for the synthesis of target molecule.
埃坡霉素A的全合成是通过连接4个片段4-7a来描述的。其中三个片段，4、5和7a，仅含有一个手性中心；所有其他手性中心都是通过简单的不对称催化反应引入的。关键步骤包括用乙炔化物8使环氧化物5开环以构建C12-C13顺式双键，以及雅各布森小组开发的用于在C3引入手性中心的实用水解动力学拆分（HKR）。特别地，通过3-O-PMB保护基的远程效应将3-O-PMB埃坡霉素C 3b进行立体选择性环氧化，得到了用于合成目标分子的高产率的C12-C13α-环氧化物。
