Studies directed towards the total synthesis of koshikalide: stereoselective synthesis of the macrocyclic core

The stereoselective synthesis of the macrolactone core of the natural product koshikalide is described. Starting with readily available 1,4-butanediol and malic acid as synthons, our synthetic strategy involved the reiterative application of Gilman’s reaction, Swern oxidation and Sharpless asymmetric epoxidation to establish the required stereocentres. Other key steps in the synthesis include Negishi cross coupling and Horner–Wadsworth–Emmons (HWE) reactions for construction of the main fragments. The 14-membered lactone ring was prepared by a selective Mitsunobu macrolactonization approach.