Total Synthesis of (-)-Cephalotaxine and (-)-Homoharringtonine via Furan Oxidation-Transannular Mannich Cyclization.

Homoharringtonine and its precursor, cephalotaxine, were synthesized. Oxidative ring-opening of a furan unveils a amine-tethered dicarbonyl, which undergoes spontaneous transannular Mannich cyclization. The cascade builds the full cephalotaxine substructure in a single operation in 60% yield. A Noyori reduction enabled synthesis of the title compounds with excellent eantioselectivity (krel = 278).