Formal total synthesis of (-)-apicularen a via transannular conjugate addition

The formal total synthesis of the myxobacteria metabolite (-)-apicularen A (1) is described. The key step involved a novel acid-mediated transannular conjugate addition of the C13 hydroxyl into the alpha,beta-unsaturated ketone in either of the macrolactones 5a or 5b to provide the same trans-pyranone 4. Conversion of 4 into the known apicularen intermediate diol 3 completed the formal synthesis.