The Stereocontrolled Total Synthesis of Altohyrtin A/Spongistatin 1: The Southern Hemisphere EF Segment

Abstract

The fully functionalised C29-C51 southern hemisphere of altohyrtin A/spongistatin 1 (1), incorporating the E- and F-ring tetrahydropyran rings and the unsaturated side chain, has been synthesised in a highly convergent and stereocontrolled manner. Key steps in the synthesis of this phosphonium salt include four highly diastereoselective, substrate-controlled, boron aldol reactions to establish key C-C bonds and accompanying stereocentres, where the introduction of the chlorodiene side chain and the C47 hydroxyl-bearing centre were realised by exploiting remote stereoinduction from the F-ring tetrahydropyran.