The polyether antibiotic salinomycin was synthesized via coupling between the C10-C17 aldehyde, (2R, 4S, 5S, 6S, 7R)-6-ethyl-5, 7-isopropylidenedioxy-2, 4-dimethylnonanal, and C18-C30 acetylenes, for example, (3R, 4R, 7S)-4, 7-bis(tert-butyldimethylsilyloxy)-7-[(2R, 5R, 6S)-5-ethyl-5-(4-methoxybenzyloxy)-6-methyltetra-hydropyran-2-yl]-3-(4-methoxybenzyloxy)oct-1-yne, followed by the aldol condensation with the C1-C9 segment, (R)-2-[(2R, 5S, 6R)-6-[(R)-1-formylethyl]-5-methyltetrahydropyran-2-yl]butanoic acid. In this total synthesis, protection of hydroxy groups with the 4-methoxybenzyl group played an important role.