Divergent Synthesis of 17-nor-Cephalotane Diterpenoids through Developed Ynol-diene Cyclization

The diversity of complex molecular structures of Cephalotaxus diterpenoids poses great challenges in uncovering the pharmaceutical potential of these natural products. As a subfamily of Cephalotaxus diterpenoids, 17-norcephalotane diterpenoids possess polycyclic frameworks with seven-membered A ring bearing different oxidation states. On the basis of a novel ynol-diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17-nor-cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)-3-deoxyfortalpinoid F, (+)-harringtonolide, (−)-fortalpinoids M/N/P, and analog (−)-20-deoxocephinoid P have been achieved in 14-17 linear longest steps starting from commercially available materials.