Convergent Total Synthesis of (-)-Cyclopamine

被引：15

作者：

Sofiadis, Manolis ^{[1
]}

Xu, Dongmin ^{[1
]}

Rodriguez, Anthony J. ^{[1
]}

Nissl, Benedikt ^{[1
]}

Clementson, Sebastian ^{[2
]}

Petersen, Nadia Nasser ^{[2
]}

Baran, Phil S. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] LEO Pharm AS, Res & Early Dev, DK-2750 Ballerup, Denmark

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2023年 / 145卷 / 40期

基金：

欧盟地平线“2020”;

关键词：

VERATRUM ALKALOID SERIES; CONSTRUCTION; CYCLOPAMINE; ALKYLATION; DESIGN; CORE; DERIVATIVES; INHIBITORS; JERVINE;

D O I：

10.1021/jacs.3c09085

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A concise and enantioselective total synthesis of the Veratrum alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a de novo synthesis of the trans-6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji-Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite diastereocontrol, and a late-stage ring-closing metathesis (RCM) reaction to forge the central tetrasubstituted olefin.

引用

页码：21760 / 21765

页数：6

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