title: Enantioselective Formal Syntheses of 11 Nuphar Alkaloids and Discovery of Potent Apoptotic Monomeric Analogues.
abstract: 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.
authors: Department of Chemistry, Dartmouth College, Hanover, NH, 03755, USA.
authors: Hui
authors: H
authors: Li
authors: Department of Chemistry, Dartmouth College, Hanover, NH, 03755, USA.
authors: Alexander
authors: A
authors: Korotkov
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine, Lebanon, NH, 03756, USA.
authors: Charles W
authors: CW
authors: Chapman
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine, Lebanon, NH, 03756, USA. alan.r.eastman@dartmouth.edu.
authors: Alan
authors: A
authors: Eastman
authors: Department of Chemistry, Dartmouth College, Hanover, NH, 03755, USA. jimmy.wu@dartmouth.edu.
authors: Jimmy
authors: http://orcid.org/0000-0002-0938-8019
authors: J
authors: Wu
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D055808:Drug Discovery; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids
keywords: alkaloids; apoptosis; cancer; natural products; organocatalysis