Open Access
Dearomative Synthetic Entry into the Altemicidin Alkaloids
Author(s) -
Claire S. Harmange Magnani,
Thomas J. Maimone
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c04147
Subject(s) - chemistry , moiety , stereochemistry , cycloaddition , combinatorial chemistry , pyridinium , structural motif , organic chemistry , biochemistry , catalysis
Altemicidin and related Streptomyces -derived monoterpene alkaloids possess dense, highly polar azaindane cores as well as potent cytotoxic and tRNA synthetase inhibitory properties. The congested α-amino acid motif decorating their presumed iridoid-like core structure has proven to be both a synthetic challenge and a biosynthetic mystery to date. Herein, we report a distinct, abiotic strategy to these alkaloids resulting in a concise synthesis of altemicidin from simple chemical feedstocks. Key chemical findings include the exploitation of a dearomative pyridinium addition and dipolar cycloaddition sequence to stereospecifically install the quaternary amine moiety, and a chemoselective molybdenum-mediated double reduction to establish the fully functionalized azaindane nucleus with minimal redox manipulations.