The olefin metathesis approach to epothilone A and its analogues

被引：160

作者：

Nicolaou, KC

He, Y

Vourloumis, D

Vallberg, H

Roschangar, F

Sarabia, F

Ninkovic, S

Yang, Z

Trujillo, JI

机构：

[1] SKAGGS INST CHEM BIOL, LA JOLLA, CA 92037 USA

[2] SCRIPPS RES INST, LA JOLLA, CA 92037 USA

[3] UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 1997年 / 119卷 / 34期

关键词：

D O I：

10.1021/ja971109i

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The olefin metathesis approach to epothilone A (1) and several analogues (39-41, 42-44, 51-57, 58-60, 64-65, and 67-69) is described. Key building blocks 6-8 were constructed in optically active form and were coupled and elaborated to olefin metathesis precursor 4 via an aldol reaction and an esterification coupling. Olefin metathesis of compound 4, under the catalytic influence of RuCl2(=CHPh)(PCy3)(2), furnished cis- and trans-cyclic olefins 3 and 48. Epoxidation of 49 gave epothilone A (1) and several analogues, whereas epoxidation of 50 resulted in additional epothilones. Similar elaboration of isomeric as well as simpler intermediates resulted in yet another series of epothilone analogues and model systems.

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页码：7960 / 7973

页数：14

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