TOTAL SYNTHESIS OF TAXOL .1. RETROSYNTHESIS, DEGRADATION, AND RECONSTITUTION

被引:195
作者
NICOLAOU, KC [1 ]
NANTERMET, PG [1 ]
UENO, H [1 ]
GUY, RK [1 ]
COULADOUROS, EA [1 ]
SORENSEN, EJ [1 ]
机构
[1] UNIV CALIF SAN DIEGO, DEPT CHEM & BIOCHEM, LA JOLLA, CA 92093 USA
关键词
D O I
10.1021/ja00107a006
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A successful strategy for the enantioselective synthesis of the natural stereoisomer of Taxol (1) has been developed. This strategy utilized the convergent assembly of Taxol's central eight-membered B ring from preformed synthons for rings A (10) and C (9) followed by late introduction of the D ring and side chain. Degradative studies confirmed the viability of certain crucial manipulations including oxidation of the C13 position (35 --> 3) and regioselective introduction of the C1-hydroxyl, C2-benzoyloxy moiety (29 --> 31). Additionally, a convenient method for the large-scale production of 29, a derivative useful for C2 analog production, was developed.
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收藏
页码:624 / 633
页数:10
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