Total synthesis of epothilone a through stereospecific epoxidation of the p-methoxybenzyl ether of epothilone C.
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.
Liu
Zhi-Yu
ZY
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, China. zhiyuliu2001@yahoo.com.cn
Chen
Ze-Cheng
ZC
Yu
Cheng-Zhi
CZ
Wang
Rui-Fang
RF
Zhang
Ru-Zhou
RZ
Huang
Chu-Sheng
CS
Yan
Zheng
Z
Cao
De-Rong
DR
Sun
Jian-Bo
JB
Li
Gang
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D034261:Epothilones; C426624:epothilone C; C093787:epothilone A