Formation of Dipeptide in the Reaction of Amino Acids with cyclo-Triphosphate

Abstract

The reaction of glycine (Gly) or L-α-alanine (Ala) with inorganic sodium cyclo-triphosphate hexahydrate (P_3m), Na₃P₃O₉·6H₂O gave dipeptides and the phosphorylated products of amino acids, but the reaction of L-valine (Val) or L-serine (Ser) with P_3m showed no peptide formation. The phosphorylated products of these reactions have a P-N bond in their molecules. Gly reacted with P_3m to give N-(carboxymethyl)phosphoramidate (P₁(N)Gly : 1a), 5-oxo-1, 3, 2-oxazaphospholidin-2-olate 2-oxide (P₁(N, O)Gly : 2a), which was a five-membered cyclic anhydride, N-(N-phosphonoglycyl)glycine (P₁-N(GlyGly) : 3a), N-(carboxymethyl)triphosphoramidate (P₃(N)Gly : 4a), and glycyl-glycine (GlyGly). A five-membered cyclic anhydride (2a) which was formed via an intramolecular cyclization of 4a was found to be a key intermediate for the production of GlyGly. Phosphorylation of Ala with P_3m also gave alanylalanine (AlaAla) in addition to the phosphorylated products including a five-membered cyclic anhydride. The yields of GlyGly and AlaAla were 15.8 and 2.0%, respectively. In the reactions of Val and Ser with P_3m, only N-(1-carboxy-2-methylpropyl)phosphoramidate (P₁-(N)Val : 1c) and N-(1-carboxy-2-hydroxyethyl)phosphoramidate (P₁-(N)Ser : 1d) were formed and their dipeptides were not obtained at all. The mechanism of the dipeptide formation will be discussed.