Selective Chemical Cleavage of Asparagine Peptides

Abstract Asparagine peptide was selectively cleaved by the Hofmann rearrangement followed by an alkaline treatment at the peptide linkage in which an amino group of the asparagine residue participated. Upon reaction of N-benzyloxycarbonyl-l-alanyl-l-asparagine with one equivalent of bromine and three equivalents of aqueous sodium hydroxide solution at 60°C, 1-(N-benzyloxycarbonyl-l-alanyl)-2-oxoimidazolidine-5-carboxylic acid was obtained in quantitative yield. When this was treated with an aqueous methanolic sodium hydroxide solution at room temperature, a cleavage reaction occurred to give N-benzyloxycarbonyl-l-alanine and 2-oxo-imidazolidine-5-carboxylic acid. Under the same condition of the rearrangement, N-benzyl-oxycarbonyl-l-asparaginyl-l-phenylalanine was converted to 1-benzyloxycarbonyl-2-oxoimidazo-lidine-5-carbonylphenylalanine. Since glutamine peptide could not give the corresponding ring compound, this cleavage reaction was found to be specific to asparagine peptide.