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

because of its potent cytotoxic activity. Its total synthesis has proven to be difficult, however, due to its

challenging structure. The influence of the configuration of a homoallylic stereocenter on the closure of a 14-

membered macrocyclic carbonate by ring-closing metathesis (RCM) from two epimeric dienes is described. The

results offer some insights into the structural features which contribute to hampering the closure of the

macrocyclic core of the macrolide polyketide. A formal synthesis of the marine macrolide (–)-callyspongiolide is

also reported using a RCM approach (C10-C11 bond formed) from analogous dienes bearing an α,β-unsaturated

ester instead of a carbonate