Studies towards the synthesis of the palmerolides

Abstract

In 2006, Baker reported the isolation of palmerolide A, a polyketide derived marine macrolide, from the Antarctic tunicate Synoicum adareanum collected in the shallow waters surrounding Anvers Island. This unique macrolide displayed potent levels of cytotoxic activity in the human melanoma cell lines (UACC-62, LC₅₀ = 18 nM and M14 LC₅₀ = 76 nM), while also inhibiting V ATPase with an IC₅₀ of 2 nM. There have been eight further palmerolides isolated from Synoicum adareanum, which have been shown to possess cytotoxicity activity. The synthetic route devised for palmerolide A, utilised a convergent approach relying on the initial synthesis of three subunits. These subunits were to be coupled via a Horner-Wadsworth Emmons reaction, a Julia-Kocienski olefination, then followed by formation of the macrolcycle. This approach offers both flexibility and convergence, as alterations to the subunits would give access to other members of the palmerolide family and their analogues such as palmerolide E.