Selectivity in the trimethylsilylation and acylation of peptide bonds, and its application to modification of the enkephalins

Abstract

N.m.r. spectra of N-acylated peptides, formed by reaction of protected peptides with silylating agents followed by acylation, have provided a means for assessing selectivity in the acylation of amide bonds. Amino-acids such as valine and phenylalanine prevent significant acylation on neighbouring amide bonds while N-acylation occurs readily at glycyl amide bonds, one residue away from a hindered centre. Selective N-acylation of the Gly-Gly bond in enkephalin derivatives has been carried out using this methodology. Trimethylsilylation of Z-protected enkephalin derivatives provide a mild method for conversion into hydantoin (2,4-dioxoimidazoline) analogues of the enkephalins.