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

Abstract

Homoharringtonine and its congener cephalotaxine were synthesized. Oxidative ring-opening of a furan unveils an 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 enantioselectivity (k_rel =278).

Keywords: Mannich reactions; alkaloids; cephalotaxine; homoharringtonine; total synthesis.