The First Total Synthesis of Topsentolide B3

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.