Concise epoxide-based synthesis of the C14–C25 bafilomycin A1 polypropionate chain

An efficient nonaldol convergent synthesis of the C14–C25 polyketide fragment of bafilomycin A1 was completed in 16% overall yield and 8 steps in its longest linear sequence. This synthesis highlights the formation of the key fragments using a three-step sequence of epoxide cleavage, alkyne reduction, and epoxidation developed in our laboratory; starting from suitably protected enantiomeric epoxides of trans-2,3-epoxybutanol. This chemistry represents a quick asymmetric and diastereoselective construction of the polyketide chain of bafilomycin A1, in which every stereogenic center was constructed using solely epoxide chemistry.