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Published on: February 24, 2015
Second-Generation Synthesis of the Male Contraceptive YCT-529
Naresh Gantasala1, Narsihmulu Cheryala1, Gunda I Georg1
1Department of Medicinal Chemistry and Institute for Therapeutics Discovery & Development, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, Minneapolis, Minnesota55414, United States.
Abstract:
We report a practical synthesis of the nonhormonal male contraceptive YCT-529. The method features key transformations: Grignard-mediated acetylation, the α-methylenation of a methyl ketone, and pyrrole formation via the Stetter and Paal-Knorr reaction sequence. It avoids iridium and palladium catalysts, overcoming the major limitations of an earlier synthesis. The current scalable synthesis proceeds in 6 steps from bromochromene 4 in 51% overall yield and does not require chromatographic purification.
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