Fluorinated C20‐ <i>epi</i> ‐Deoxysalinomycin Derivatives: Synthesis and Evaluation of Anticancer Activities

Salinomycin exhibits potent cytotoxic activity against various cancer types. Leveraging the advantages of fluorination in drug development, we efficiently synthesized 17 fluorinated C20-epi-deoxysalinomycin derivatives through a streamlined 4-5 step synthetic route. Key transformations, including room-temperature azidation, copper-catalyzed click reactions, and amide condensation, were performed under mild conditions with satisfactory yields. Cytotoxicity analysis revealed that the fluorinated salinomycin derivative 5f exhibited superior potency and selectivity, underscoring its potential as a novel antitumor agent and highlighting the effectiveness of fluorination in salinomycin-based therapeutics development.