Total syntheses of epothilones A and B via a macrolactonization-based strategy

被引:214
作者
Nicolaou, KC
Ninkovic, S
Sarabia, F
Vourloumis, D
He, Y
Vallberg, H
Finlay, MRV
Yang, Z
机构
[1] SCRIPPS RES INST, LA JOLLA, CA 92037 USA
[2] SKAGGS INST CHEM BIOL, LA JOLLA, CA 92037 USA
[3] UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA
关键词
D O I
10.1021/ja971110h
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The total syntheses of epothilones A (1) and B (2) and several analogues thereof are described. The reported strategy relies on a macrolactonization approach and features selective epoxidation of the macrocycle double bond in precursors 3 and 4 (Scheme 1), respectively, as well as high convergency and flexibility. Building blocks 9-12 and 15 were constructed by asymmetric processes and coupled via Wittig, aldol, and macrolactonization reactions to afford the basic skeleton of epothilones and that of several of their analogues by a relatively short route. The utilization of intermediate 14, obtained via a stereoselective Wittig reaction and its Enders coupling to SAMP hydrazone 13 (Scheme 8), in combination with a stereoselective aldol reaction with the modified substrate 69 (Scheme 10) improved the stereoselectivity and efficiency of the total synthesis of these new and highly potent microtubule binding antitumor agents.
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页码:7974 / 7991
页数:18
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