Divergent Total Syntheses of Rearranged Steroids Swinhoeisterols A-C
Ganlin Huang1, Xinliang Zhang1, Yu-Cheng Gu2
1State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Abstract:
Swinhoeisterols A-C are 13(14→8),14(8→7)-diabeo-steroids possessing an intriguing 6/6/5/7 tetracyclic core framework and potent inhibitory activity against the histone acetyltransferase p300. Herein we report their divergent total syntheses from readily available (S)-Wieland-Miescher ketone. A tandem Negishi/Heck cross-coupling of a chloroenol triflate was developed to install the labile methylenecyclopentene motif using a silyl-tethered homoallylic zinc reagent that was carefully designed to suppress undesired [Pd]-H insertion. Furthermore, a Baran reductive olefin coupling of a diene, a rarely used radical donor, with a tethered acrylonitrile group allowed for the simultaneous construction of the seven-membered ring and two contiguous stereocenters, including a quaternary carbon center.
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