Synthesis of C3-C12 Fragment of 24-Demethylbafilomycin C1 via anti-Selective Aldol Condensation as the Key Stereocontrol Step

Abstract

An efficient synthesis of the C3-C12 aldehyde fragment of 24-demethylbafilomycin C 1 was accomplished for assembling the 16-membered plecomacrolide skeleton according to a 1,3-diene-ene ring-closing metathesis (RCM) strategy. A boron-mediated ANTI-selective aldol condensation of Abiko’s chiral propionate was used to secure the C6 and C7 stereogenic centers while the C8 chirality was introduced from a chiral building block. The dithiane alkylation and the methyl ketone Horner-Wittig olefination using allyldiphenylphosphine oxide were employed for construction of the requisite ( E)-1,3-diene subunit.