Total Synthesis of Pulvomycin D

A synthetic route to the pulvomycin class of natural products is presented, which culminated in the first synthesis of a pulvomycin, pulvomycin D. Key elements of the strategy include a pivotal aldol reaction which led to bond formation between the C24‐C40 and the C8‐C23 fragment. The remaining C1‐C7 fragment was attached by a Yamaguchi esterification completing the assembly of the 40 carbon atoms within the main skeleton. Ring closure to the 22‐membered lactone ring was achieved in the final stages of the synthesis by a Heck reaction. The completion of the synthesis required the removal of six silyl protecting groups in combination with olefin formation at C26‐C27 by a Peterson elimination.