The use of the Nbb-resin for the solid-phase synthesis of peptide alkylesters and alkylamides. Synthesis of leuprolide

The use of nucleophiles for the cleavage of an o-nitrobenzylester peptide-resin bond in order to afford peptide alkylesters and alkylamides has been studied. With this purpose, three short peptide sequences anchored to a Nbb-resin were used as models. Peptides were cleaved from the polymeric supports by reaction with primary and secondary amines and by a transesterification process with yields that depended on the nucleophile and the C-terminal amino acid of the sequence. This methodology was applied to the synthesis of leuprolide, an ethylamide peptide of relevant pharmacological interest, which was obtained in a 70% overall yield. (C) 1997 Elsevier Science Ltd.