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.