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A Divergent Enantioselective Total Synthesis of Post‐Iboga Indole Alkaloids
Author(s) -
Zhou Jie,
Tan DongXing,
Han FuShe
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202008242
Subject(s) - enantioselective synthesis , indole test , chemistry , intramolecular force , stille reaction , total synthesis , stereochemistry , ring (chemistry) , stereoselectivity , aldol reaction , indole alkaloid , divergent synthesis , catalysis , combinatorial chemistry , organic chemistry
Abstract Divergent enantioselective total syntheses of five naturally occurring post‐iboga indole alkaloids, dippinine B and C, 10,11‐demethoxychippiine, 3‐ O ‐methyl‐10,11‐demethoxychippiine, and 3‐hydroxy‐3,4‐secocoronaridine, as well as the two analogues 11‐demethoxydippinine A and D, are presented for the first time. The enantioenriched aza[3.3.1]‐bridged cycle, a common core intermediate to the target molecules, was constructed through an asymmetric phase‐transfer‐catalyzed Michael/aldol cascade reaction. The challenging azepane ring fused around the indole ring and the [3.3.1]‐bridged cycle were installed through an intramolecular S N 2′‐type reaction. These cyclization strategies enabled rapid construction of the [6.5.6.6.7]‐pentacyclic core at an early stage. Highlights of the late‐stage synthetic steps include a Pd‐catalyzed Stille coupling and a highly stereoselective catalyst‐controlled hydrogenation to incorporate the side chain at C 20 with both R and S configurations in the natural products.