Enantioselective Formal Syntheses of 11 Nuphar Alkaloids and Discovery of Potent Apoptotic Monomeric Analogues
Hui Li
Department of Chemistry, Dartmouth College, Hanover, NH, 03755 USA
Search for more papers by this authorDr. Alexander Korotkov
Department of Chemistry, Dartmouth College, Hanover, NH, 03755 USA
Search for more papers by this authorCharles W. Chapman
Department of Pharmacology and Toxicology, Geisel School of Medicine, Lebanon, NH, 03756 USA
Search for more papers by this authorCorresponding Author
Prof. Alan Eastman
Department of Pharmacology and Toxicology, Geisel School of Medicine, Lebanon, NH, 03756 USA
Search for more papers by this authorCorresponding Author
Prof. Jimmy Wu
Department of Chemistry, Dartmouth College, Hanover, NH, 03755 USA
Search for more papers by this authorHui Li
Department of Chemistry, Dartmouth College, Hanover, NH, 03755 USA
Search for more papers by this authorDr. Alexander Korotkov
Department of Chemistry, Dartmouth College, Hanover, NH, 03755 USA
Search for more papers by this authorCharles W. Chapman
Department of Pharmacology and Toxicology, Geisel School of Medicine, Lebanon, NH, 03756 USA
Search for more papers by this authorCorresponding Author
Prof. Alan Eastman
Department of Pharmacology and Toxicology, Geisel School of Medicine, Lebanon, NH, 03756 USA
Search for more papers by this authorCorresponding Author
Prof. Jimmy Wu
Department of Chemistry, Dartmouth College, Hanover, NH, 03755 USA
Search for more papers by this authorAbstract
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.
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