Direct Conversion of Resin-Bound Peptides to C-Terminal Esters

Abstract

A mild and effective method was developed to convert peptides immobilized on the 2-chlorotrityl and Wang resins directly to C-terminal esters. After conventional Fmoc peptide synthesis, treatment with anhydrous HCl (0.2-3 M) in a variety of alcohols was shown to produce the corresponding peptide esters in good yield and purity. Under the mildest conditions investigated, acid-sensitive protection groups such as N-Boc, trityl, tert-butyl ether, tert-butyl ester, and Pbf remain intact.