Total Synthesis of (-)-Cephalotaxine Using a Radical Cascade

Abstract

(–)-Cephalotaxine, which was isolated from Cephalotaxus harringtonia, has attracted much attention from many chemists due to a combination of its fascinating pentacyclic structure and the antileukemic activity of its ester derivatives such as harringtonine and homoharringtonine. Herein, a very short synthesis of (–)-cephalotaxine using the same radical cascade strategy is described. Treatment of radical precursor, which was readily prepared from diethyl D-tartrate, with Bu₃SnH/ACN caused radical cascade involving 7-endo-trig/5-endo-trig cyclization to afford a pentacyclic system of (–)-cephalotaxine. After the removal of protective groups, the resulted diol was oxidized to afford diketone. Synthesis of (–)-cephalotaxine was accomplished by selective O-methylation of diketone followed by reduction of two carbonyl groups.