Total Synthesis of the Antiproliferative Macrolide (+)-Neopeltolide

A concise total synthesis of the very promising antiproliferative macrolide (+)-neopeltolide (1) has been performed in 16 steps. The main steps of this approach are a Ru^II-catalyzed alkyne−enal coupling, a Pd⁰-catalyzed desulfurative cross-coupling, and a stereoselective In^III-catalyzed propargylation. Four stereogenic centers out of six have been set thanks to substrate-controlled diastereoselective reactions with minimal reliance on protecting groups.