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Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone.

Lian-Dong GuoJieping HouWentong TuYan ZhangYue ZhangLouxi ChenJing Xu
Published in: Journal of the American Chemical Society (2019)
The intriguing structural complexity and bioactivities of the Daphniphyllum alkaloids have long attracted much attention. Herein, we report the first and enantioselective total synthesis of Daphniphyllum alkaloid dapholdhamine B and its lactone derivative. The chemical structure of dapholdhamine B contains a unique aza-adamantane core skeleton and eight contiguous stereocenters, including three contiguous fully substituted stereocenters, which present a formidable synthetic challenge. This concise approach used to achieve the first synthesis of an aza-adamantane natural product features a vinylogous Mannich reaction, an optimized α-bromo-α,β-unsaturated ketone synthesis, a substrate-dependent intramolecular aza-Michael addition, a key annulation via amide activation, an SN2'-type lactonization, and a facile Horner-Wadsworth-Emmons reaction that converts the hemiacetal moiety to the corresponding homologated carboxylic acid.
Keyphrases
  • molecular docking
  • quantum dots
  • electron transfer