Asymmetric total synthesis of cephanolide B

The asymmetric synthesis of cephanolide B, a complex C-18 Cephalotaxus dinorditerpenoid, is presented for the first time. The synthesis relies on the key hexahydrofluorenone core skeleton (A-B-C ring). A remote hydroxyl group directed hydrogenation strategy was developed to selectively reduce the tetra-substituted enone unit. A sequence of modified transformations, including single electron reduction, Barton-McCombie radical deoxygenation, lactonization, and cation mediated Friedel-Crafts cyclization, were efficiently employed to achieve the target.

Automated summary

The asymmetric synthesis of the complex C-18 Cephalotaxus dinorditerpenoid cephanolide B was achieved for the first time using a remote hydroxyl group directed hydrogenation strategy and a sequence of modified transformations. The key hexahydrofluorenone core skeleton and selective reductions were crucial in achieving the target compound.