Indexed on: 07 May '05Published on: 07 May '05Published in: Journal of Organic Chemistry
[reactions: see text] An efficient and general solution-phase method for the site-specific N-methylation of peptides has been developed. This novel procedure involves synthesis of N-nosyl protected peptides and their subsequent N-methylation with diazomethane. Its efficiency was proved by the successful synthesis of various hindered oligopeptides containing N-methyl amino acid residues with excellent yield and purity. The method is particularly attractive in that the adopted conditions do not cause any detectable racemization of the peptide stereocenters and the process does not require chromatographic purification of the methylated products. A further advantage is the compatibility of this methodology with Fmoc solution-phase peptide synthesis.