Modular synthesis of the C9-C27 degradation product of aflastatin A via alkyne-epoxide cross-couplings

A modular approach to the synthesis of complex polyketide natural products is demonstrated for the synthesis of the C9-C27 degradation product from aflastatin A. The product of the cross-coupling of C23-C27 terminal alkyne with C17-C22 epoxide underwent functionalization of the resulting internal alkyne, which was then coupled similarly with C9-C16 epoxide. This synthesis concluded with regio- and stereoselective addition of methyl onto the internal alkyne followed by stereoselective hydroboration-oxidation.