Synthesis of the Bis-tetrahydropyran Core of Amphidinol 3

A convergent synthesis of the C31-C52 bis-tetrahydropyran core of the natural product amphidinol 3 is reported. A common intermediate was synthesized from d-tartaric acid utilizing an asymmetric glycolate alkylation/ring-closing metathesis sequence to construct the THP rings. Differential elaboration of the common intermediate allowed the synthesis of two distinct coupling partners which were joined through a modified Horner-Wadsworth-Emmons olefination to provide the bis-tetrahydropyran core.