Through systematic optimization of halopyridinium compounds, we established a peptide coupling protocol utilizing 4-iodine -methylpyridinium () for solid-phase peptide synthesis (SPPS). The coupling reagent is easily prepared, bench stable, and cost-effective. Employing in the SPPS process has showcased remarkable chemoselectivity and efficiency, effectively eliminating racemization and epimerization. This achievement has been substantiated through the successful synthesis of a range of peptides via the direct utilization of commercially available amino acid substrates for SPPS.
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