Synthesis of Phosphinic Pseudomethionyl-Glutamyl-Histidine

The amidoalkylation of a phosphonous acid containing a structural isostere of diethyl glutamiate, using ethyl carbamate and 3-(methylthio)propionaldehyde, was proposed for the synthesis of NC(O)OEt-protected phosphinic pseudo-Met-Glu-peptide. Subsequent adamantyl protection of the phosphorylic function and hydrolysis of carboxylic groups made it possible to obtain phosphinic Met-[P]-Glu peptide in the form of cyclic glutamate anhydride. It was found that the latter reacts with the third amino acid component histidine to form the phosphinic Met-[P]-Glu-gamma-His tripeptide.