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Enantioselective Formal Syntheses of 11 Nuphar Alkaloids and Discovery of Potent Apoptotic Monomeric Analogues
Author(s) -
Li Hui,
Korotkov Alexander,
Chapman Charles W.,
Eastman Alan,
Wu Jimmy
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201600106
Subject(s) - enantioselective synthesis , chemistry , stereochemistry , natural product , monomer , stereoisomerism , formal synthesis , drug discovery , molecule , organic chemistry , catalysis , biochemistry , polymer
Concise, scalable, and enantioselective formal syntheses of eight dimeric and three monomeric nuphar alkaloids were achieved, along with the construction of a stereochemically diverse collection of the first known monomeric analogues having apoptotic activity. The syntheses involved the development of highly enantioselective Brønsted acid catalyzed vinylogous Mukaiyama–Mannich reactions, which feature the unprecedented use of a supersilyl group to control the regio‐, enantio‐ and diastereoselectivity. Biological studies reveal that several of these novel nuphar analogues are even more potent than their dimeric natural product counterparts.