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One‐Step Multigram‐Scale Biomimetic Synthesis of Psiguadial B
Author(s) -
Newton Christopher G.,
Tran Duc N.,
Wodrich Matthew D.,
Cramer Nicolai
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201708333
Subject(s) - chemistry , stereocenter , natural product , quinone methide , benzaldehyde , cascade reaction , biomimetic synthesis , intramolecular force , cationic polymerization , michael reaction , stereochemistry , cascade , combinatorial chemistry , enantioselective synthesis , catalysis , quinone , organic chemistry , chromatography
A gram‐scale synthesis of psiguadial B, a purported inhibitor of human hepatoma cell growth, has been achieved in one step by a biomimetic three‐component coupling of caryophyllene, benzaldehyde, and diformylphloroglucinol. This cascade reaction is catalyzed by N,N′‐dimethylethylenediamine, and proceeds at ambient temperature to generate four stereocenters, two rings, one C−O bond, and three C−C bonds. Combined computational and experimental investigations suggest the biosynthesis of the natural product is non‐enzyme mediated, and is the result of a Michael addition between caryophyllene and a reactive ortho‐quinone methide, followed by two sequential intramolecular cationic cyclization events.