Pursuing Step Economy in Total Synthesis of Complex Marine Macrolide Natural Products

Here I describe our first-, second-, and third-generation synthesis of (+)-neopeltolide, which is a Jamaican marine macrolide that shows potent antiproliferative and antifungal activities. The third-generation synthesis enabled an expedient access to (+)-neopeltolide in 11 linear and 23 total steps, which is so far the shortest synthesis of this natural product. Convergent synthesis planning by taking advantage of chemoselective transformations, cross-coupling reactions, and tandem reactions was the key for increasing step economy.