Highly stereocontrolled total synthesis of the polyether antibiotic salinomicin. II. Synthesis of right (C18-C30) segments from D-glucose, D-mannitol, and ethyl L-lactate.

Abstract

(S)-4[(2R, 5R, 6S)-5-Ethyl-5-hydroxy-6-methyltetrahydropyran-2-yl]pentan-4-olide (5), an alkaline degradation product of salinomycin (1), was synthesized with complete stereoselectivity from D-mannitol and ethyl L-lactate.Compound 5 was then converted to (3R, 4S, 7S)-7-[(2R, 5R, 6S)]-5-ethyl-5-methoxymethoxy-6-methyltetrahydropyran-2-yl]-4, 7-bismethoxymethoxy-3-(tetrahydropyran-2-yloxy)oct-1-yne (3), a C18-C30 segment of 1, via Sharpless asymmetric epoxidation. Another C18-C30 segment, (R)-3-[2RS, 5S]-5-[(2R, 5R, 6S)-5-benzyloxy-5-ethyl-6-methyltetrahydropyran-2-yl]-2-methoxy-5-methyltetrahydrofuran-2-yl]-3-(4-methoxybenzyloxy)prop-1-yne (4), was synthesized more conveniently via coupling between a C19-C22 fragment prepared starting from D-glucose and a C23-C30 fragment prepared starting from D-mannitol and ethyl L-lactate.