Reactivity of dehydroaspartic acid derivatives under peptide coupling conditions

Article abstract of DOI:10.1016/S0040-4039(00)79048-4

The reactivity of α-carboxy-activated dehydroaspartic acid derivatives with various N- and O-nucleophiles is described for the first time. Reaction of amino acid derivatives with Ac-Δ(Z)Asp(OBu(t))-OH (4a) under a variety of coupling conditions gave very poor yields of the resulting dehydroaspartyl dipeptides, while the coupling of 4a with oxygen nucleophiles gave very good yields of the dehydroaspartyl esters. In contrast, the coupling of amino acids with Cbz-Δ(Z)Asp(Obu(t))-OH (4b) gave good yields of dehydroaspartyl dipeptides. The formation of a highly reactive oxazolone intermediate is proposed to explain the low yields of peptide coupling between 4a and amino acids.