Novel and Efficient Synthesis of the Promising Drug Candidate Discodermolide

摘要

In a novel approach to the potential antitumor drug discodermolide, we have prepared new 'stereotriad building blocks' and used them to build one of two key intermediates. We prepared the other critical intermediate, the so called 'stereopentad,' by degradation of oleandomycin. We also modified the 'building block' synthesis in order to prepare 'anti, anti' stereotriads and we developed a new route to polypropionate building blocks that bear a Z-vinyl iodide or an E-vinyl iodide. We showed that proper choice of catalyst allows the reduction of a propargyl alcohol to a Zallylic alcohol in the presence of a vinyl iodide. Thus we have shown the viability of all high-risk steps in the total synthesis.