Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for Enantioselective Total Synthesis of Mavacuran Alkaloids

Reported is the enantioselective total syntheses of mavacuran alkaloids, (+)‐taberdivarine H, (+)‐16‐hydroxymethyl‐pleiocarpamine, and (+)‐16‐epi‐pleiocarpamine, and their postulated biosynthetic precursor 16‐formyl‐pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice si...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-07, Vol.58 (29), p.9861-9865
Main Authors: Jarret, Maxime, Turpin, Victor, Tap, Aurélien, Gallard, Jean‐François, Kouklovsky, Cyrille, Poupon, Erwan, Vincent, Guillaume, Evanno, Laurent
Format: Article
Language:English
Subjects:
Aliphatic compounds
Alkaloids
biosynthesis
Chemical Sciences
Conformation
Coupling
Enantiomers
Indoles
Masks
natural products
Nitrogen
Organic chemistry
oxidation
total synthesis
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Summary:Reported is the enantioselective total syntheses of mavacuran alkaloids, (+)‐taberdivarine H, (+)‐16‐hydroxymethyl‐pleiocarpamine, and (+)‐16‐epi‐pleiocarpamine, and their postulated biosynthetic precursor 16‐formyl‐pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline. Inspired by the biosynthetic hypothesis, an oxidative coupling approach from the geissoschizine framework to form the N1−C16 bond was explored. Quaternization of the aliphatic nitrogen center was key to achieving the oxidative coupling induced by KHMDS/I2 as it masks the nucleophilicity of the aliphatic nitrogen center and locks in the required cis conformation. Skeleton assembly: The long‐standing problem of effecting the bioinspired oxidative cyclization of geissoschizine to the mavacuran skeleton has been resolved. The key N1−C16 bond was formed by locking in the cis conformation through quaternization of the aliphatic nitrogen atom, and allowed the total syntheses of (+)‐taberdivarine H, (+)‐16‐hydroxymethyl‐pleiocarpamine, and (+)‐16‐epi‐pleiocarpamine, and their postulated biosynthetic precursor 16‐formyl‐pleiocarpamine.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201905227