Asymmetric Total Synthesis of Cephalotaxus Diterpenoids: Cephinoid P, Cephafortoid A, 14- epi-Cephafortoid A and Fortalpinoids M-N, P

J Am Chem Soc. 2023 Aug 9;145(31):16988-16994. doi: 10.1021/jacs.3c05455. Epub 2023 Jul 26.

Abstract

The asymmetric total syntheses of cephalotaxus C19 diterpenoids, bearing a unique cycloheptene A ring with a chiral methyl group at C-12, were disclosed based on a universal strategy. Six members, including cephinoid P, cephafortoid A, 14-epi-cephafortoid A and fortalpinoids M-N, P, were accomplished for the first time. The concise approach relies on two crucial steps: (1) a Nicholas/Hosomi-Sakurai cascade reaction was developed to efficiently generate the cycloheptene ring bearing a chiral methyl group; (2) an intramolecular Pauson-Khand reaction was followed to facilitate the construction of the complete skeleton of target molecules. Our studies provide a new strategy for the synthetic analysis of cephalotaxus diterpenoids and structurally related polycyclic natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cephalotaxus* / chemistry
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Models, Molecular

Substances

  • Diterpenes