Premium
Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for Enantioselective Total Synthesis of Mavacuran Alkaloids
Author(s) -
Jarret Maxime,
Turpin Victor,
Tap Aurélien,
Gallard JeanFrançois,
Kouklovsky Cyrille,
Poupon Erwan,
Vincent Guillaume,
Evanno Laurent
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201905227
Subject(s) - enantioselective synthesis , chemistry , oxidative coupling of methane , hydroxymethyl , indole test , stereochemistry , nucleophile , oxidative phosphorylation , biomimetic synthesis , organic chemistry , catalysis , biochemistry
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/I 2 as it masks the nucleophilicity of the aliphatic nitrogen center and locks in the required cis conformation.