Synthesis of the C3–14 fragment of palmerolide A using a chiral pool based strategy

Palmerolide A, a potent and selective inhibitor of melanoma cell growth, is a macrocylic polyketide isolated from the Antarctic tunicate Synoicum adareanum. Palmerolide A targets transmembrane proton pumps, the vacuolar-ATPases, and induces autophagy, but in a manner independent of HIF-1α activation. Herein we report a synthesis of the C3–14 fragment of palmerolide A using readily available polyols as chiral building blocks for entry into structure/activity studies of the macrocycle.