Total synthesis of trans-dihydronarciclasine through a highly endo-selective Diels-Alder cycloadditions of 3,5-dibromo-2-pyrone

Abstract

trans-Dihydronarciclasine 4, isolated by Pettit and coworkers from the Chinese medicinal plant Zephyranthes candida in 1990, is a highly potent anti-cancer agent, exhibiting two- to ten-fold higher potency than pancratistatin against selected human cancer cell lines. Utilizing a highly endo-selective Diels-Alder cycloaddition of 3,5-dibromo-2-pyrone with styrene dienophile, we have achieved the first total synthesis of (±)-trans-dihydronarciclasine in 11 steps and 15.8% overall yield.