Highly Stereocontrolled Total Synthesis of the Polyether Antibiotic Salinomycin. I. Synthesis of the Left (C1-C9) and Middle (C10-C17) Segments from D-Glucose

Abstract

The required left (C1-C9) segment, (R)-2-[(2R, 5S, 6R)-6-[(R)-1-formylethyl]-5-methyltetrahydropyran-2-yl]butanoic acid, for a total synthesis of salinomycin was highly stereoselectively synthesized from D-glucose via a chelation-controlled Grignard reaction and a decarbonylation with Wilkinson's catalyst as important steps. The stereoselective synthesis of the middle (C10-C17) segment, (2R, 4S, 5S, 6R)-6-ethyl-2, 4-dimethyl-7-oxononan-5-olide, starting from D-glucose is also described.