Oxidative Coupling Approach to Sarpagine Alkaloids: Total Synthesis of (-)-Trinervine, Vellosimine, (+)-Normacusine B, and (-)-Alstomutinine C

被引：3

作者：

Zhang, Ye ^{[1
,2
]}

Zhang, Lei ^{[2
]}

Qi, Xiangbing ^{[1
,2
,3
]}

机构：

[1] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

[2] Natl Inst Biol Sci, Beijing 102206, Peoples R China

[3] Tsinghua Univ, Tsinghua Inst Multidisciplinary Biomed Res, Beijing 100084, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2023年 / 62卷 / 28期

基金：

中国国家自然科学基金;

关键词：

Iodine; Oxidative Coupling; Rearrangement; Sarpagine Alkaloids; Total Synthesis; ENANTIOSELECTIVE TOTAL-SYNTHESIS; ENANTIOSPECIFIC TOTAL-SYNTHESIS; INDOLE ALKALOIDS; GENERAL-APPROACH; UNIFIED STRATEGY; CONSTRUCTION; OXINDOLES; KETONE;

D O I：

10.1002/anie.202304435

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Sarpagine alkaloids are bioactive indole natural products that contain a highly rigid indole-fused 1-azabicyclo[2.2.2]octane, more than 100 members of which have been identified. Herein, a detailed examination of the intramolecular oxidative coupling between a ketone and a Weinreb amide for assembling the complex 1-azabicyclo[2.2.2]octane core structure of sarpagine family alkaloids is described. Precise late-stage manipulations of the ketone and Weinreb amide enable the divergent syntheses of (-)-trinervine, (+)-vellosimine, (+)-normacusine B, and (-)-alstomutinine C. Other notable transformations of the synthesis featured an aza-Achmatowicz/indole cyclization cascade to generate the azabicyclo[3.3.1]nonane structure, a regioselective elimination reaction to form the ethylidene motif embedded in the (+)-vellosimine and (+)-normacusine B structures, and a diastereoselective indole oxidative rearrangement to form the spirooxindole structure in (-)-alstomutinine C.

引用

页数：8