Concise Means for Accessing an Advanced Precursor to 1-Deoxypaclitaxel

摘要

A program directed toward a total synthesis of 1-deoxypaclitaxel is described.The most direct route consists of six steps from the previously described diketone 12 and proceeds in 18% overall yield.The transformations involved in reaching the target molecule 22 consist of stereoselective a-ketol generation,an EtAlCl2-catalyzed transannular hydride shift,regioselective monomesylation,and a Wagner-Meerwein 1,2-shift.The central issue of this synthesis is the sequential deployment of these highly controlled steps along the perimeter and across the interior gap of a nine-membered ring.