Synthetic Studies Of Cephalotaxine

Cephalotaxine(CET)and drupacine derivatives,a kind of Cephalotaxus alkaloids with unique structure and biological activities,are widely distributed in the southern part of East Asia and the northern part of the Indochina Peninsula.Considered from the structure,CET and its derivatives process a unique benzazepine-bearing pentacyclic ABCDE-ring skeleton including a [7,5] fused ring system and an unique aza-spiro [5,5] ring system,which are rare in the natural alkaloids.Naturally occurring esters of CET(harringtonine and homoharringtonine)have been observed to be highly effective for the treatment of acute human leukemia and are currently undergoing clinical trials.The unique structure and the therapeutic potential of this group of alkaloids have stimulated much synthetic research.Nonetheless,an even more efficient and practical synthesis of CET is still highly desirable.From the structural analysis of Cephalotaxine,we designed a synthetic route featuring a cascade reaction of a Pauson-Khand reaction and an aza-Michael reaction to establish the five-membered ring in one step.Another method was based on a Pauson-Khand reaction of allene,a nitrogen alkylation reaction of enamide and an intramolecular Heck coupling reaction to accomplish the formal synthesis of Cephalotaxine.