Ring-closing metathesis studies in the context of the formal synthesis of themarine macrolide (–)-callyspongiolide

Abstract

Attempts to synthesize the natural product macrolide polyketide (–)-callyspongiolide have drawn great interest</p><p>because of its potent cytotoxic activity. Its total synthesis has proven to be difficult, however, due to its</p><p>challenging structure. The influence of the configuration of a homoallylic stereocenter on the closure of a 14-</p><p>membered macrocyclic carbonate by ring-closing metathesis (RCM) from two epimeric dienes is described. The</p><p>results offer some insights into the structural features which contribute to hampering the closure of the</p><p>macrocyclic core of the macrolide polyketide. A formal synthesis of the marine macrolide (–)-callyspongiolide is</p><p>also reported using a RCM approach (C10-C11 bond formed) from analogous dienes bearing an α,β-unsaturated</p><p>ester instead of a carbonate