Catalytic Asymmetric Synthesis of Palmerolide A via Organoboron Methodology

摘要

Numerous natural products and their synthetic derivatives are used as pharmaceutical drugs. Ongoing efforts to identify new substances with extraordinary properties have recently uncovered palmerolide A (1), a complex polyunsaturated macrolide isolated by Baker and co-workers from a marine invertebrate (Synoicum adareanum) found in the Antarctic Ocean. Palmerolide A embeds five stereogenic centers and seven unsaturations, including a dienamide. It demonstrates a very potent and unusually selective antitumor activity when assayed with melanoma cell lines, and its potency is ascribed to a low-nanomolar inhibition of vacuolar ATPase. The need for treatment of metastatic melanoma is dire, as few cancers are as aggressive and current chemotherapies are rarely effective.