A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine)

作者:Kou Kevin G M; Pflueger Jason J; Kiho Toshihiro; Morrill Louis C; Fisher Ethan L; Clagg Kyle; Lebold Terry P; Kisunzu Jessica K*; Sarpong Richmond*
来源:Journal of the American Chemical Society, 2018, 140(26): 8105-8109.
DOI:10.1021/jacs.8b05043

摘要

The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type.

  • 出版日期2018-7-4