New methods and reagents in organic synthesis. 69. A new synthesis of .ALPHA.-amino acid and peptide amides of aromatic amines using a modified Curtius reaction with diphenyl phosphorazidate.

Abstract

As a basic study on the efficient synthesis of chromogenic and fluorogenic peptidase substrates, we investigated possible general methods for the synthesis of .alpha.-amino acid and peptide amides of aromatic amines. Preparation of Boc-L-Leu-pNA (1) as a model compound was attempted by (1) the coupling of Boc-L-Leu-OH with p-nitroaniline, (2) the reaction of Boc-L-Leu-OH with p-nitrophenyl isocyanate, and (3) the reaction of Boc-L-Leu-OH with the product formed from p-nitrobenzoic acid through the modified Curtius reaction with diphenyl phosphorazidate ((C6H5O)2P(O)N3) in a one-pot process. The third method was found to be a general and efficient method for the preparation of .alpha.-amino acid amides of aromatic amines. Application of this method to the preparation of a peptidase substrate. Bz-L-Ile-L-Glu(OMe)-Gly-L-Arg-pNA (2), has also been successfully achieved.