Chemoenzymatic asymmetric total synthesis of naturally occurring resorcylic acid lactones hamigeromycins F and G

Abstract

Asymmetric total synthesis of two naturally occurring resorcylic acid lactones (RALs), hamigeromycins F and G, was achieved for the first time. The synthetic strategy involved a late-stage intramolecular macrolactonization achieved with a transesterification reaction. Stereocenters (C_10′ and C_6′) in both the molecules were accessed via an enzymatic kinetic resolution reaction. The penta-substituted aromatic core present in hamigeromycins F and G was accessed using vanillin as a precursor. The crucial E-olefinic unsaturated bond at C_1′–C_2′ was constructed with a stereoselective Julia–Kocienski olefination reaction.