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

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.