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 pept ide-resin bond in order to afford peptide alkylesters and alkylamides has been studied. With this purpose, three short peptide sequences anc hored to a Nbb-resin were used as models. Peptides were cleaved from t he polymeric supports by reaction with primary and secondary amines an d by a transesterification process with yields that depended on the nu cleophile and the C-terminal amino acid of the sequence. This methodol ogy was applied to the synthesis of leuprolide, an ethylamide peptide of relevant pharmacological interest, which was obtained in a 70% over all yield. (C) 1997 Elsevier Science Ltd.