A LOW-EPIMERIZING PEPTIDE COUPLING REAGENT BASED ON THE REARRANGEMENTOF A CARBOXYLIC-SULFONIC MIXED ANHYDRIDE

A series of peptides has been prepared using an o-hydroxybenzenesulfon yl chloride as the condensation reagent. Experimentally, the coupling is a one pot two-steps reaction: formation and aminolysis of a substit uted aryl ester. The first step occurs by an elimination-addition reac tion involving a sulfoquinone intermediate, followed by an efficient s ix-membered acyl transfer reaction in the phenolic carboxylic-sulfonic mixed anhydride intermediate. The Young and Anteunis tests show that the degree of epimerization is very low in methylene chloride and acet onitrile.