Synthesis of C1–C15 of palmerolide A: tactical advances that can lead to better design strategies for polyketide synthesis

Abstract

A streamlined synthesis of a C1–C15 fragment of palmerolide A is described. Key tactical advances (vis-à-vis previous reports from the Dudley laboratory) include diastereoselective reduction (>20:1 dr) of a C7 ketone using DIP chloride and a modified protecting group strategy that enables both improved step count and end-game efficiency. Asymmetric reduction of linear alkyl vinyl ketone derivatives is a largely unsolved problem in organic synthesis. DIP chloride has been uniquely effective for asymmetric reduction of the alkyl vinyl ketone derivatives in the present study.