Triphenyl Phosphite-Mediated One-Pot Peptide-Bond Formation under Neutral Reaction Conditions

Liquid-phase peptide synthesis requires an excessive amount of strong C-terminal-activating reagents under acidic or basic conditions. Although the reaction proceeds well, it is accompanied by epimerization and other side reactions with active reagents, necessitating stepwise purification. Herein, we present an efficient peptide bond formation using P(OPh)3, which yields the corresponding peptides in high yield, and diastereopurity. In addition, this atom-economical method under neutral conditions minimizes side reactions and facilitates seamless one-pot oligopeptide synthesis.