The First Total Synthesis of Topsentolide B₃

Abstract

Abstract The first total synthesis of the cytotoxic oxylipin Topsentolide B 3 has been accomplished in 15 steps with an overall yield of 24 %. Starting with readily available cis ‐butene diol as a synthon, the synthesis involved Marouka allylation and Sharpless hydroxylation for the construction of three asymmetric centers. The nine‐membered lactone ring was built through a selective Grubbs ring‐closing metathesis reaction. Other key steps in the synthesis are Cu I ‐mediated alkynylation and Swern oxidation reactions. This provides a unique approach to the synthesis of oxylipins and offers the advantages of brevity and relatively high overall yield.