Résumé
Recent developments in peptide synthesis have underlined the importance of optimising, on a preparative scale, the
N
-carbamoylation of amino acids by aqueous cyanate. To this purpose, a theoretical model of aqueous cyanate reactivity was designed. The parameters of the model were evaluated, for various pH and temperatures, from a critical survey of the literature, together with additional experimental data. Computer-simulated kinetics based on this model showed the reaction efficiency to be significantly dependent on pH, and suggested optimum conditions to be moderate temperatures and pH 8.5-9. Discussion of the practical convenience of these theoretical results led us to prefer 40-50 °C and a pH range of 7-8 as reaction conditions, thus maintaining reaction times within a few hours. Various
N
-carbamoyl amino acids (ureido derivatives of glycine,
L
-valine,
L
-alanine,
L
-leucine,
DL
-methionine,
N
-trifluoroacetyl-
L
-lysine, β-alanine) were thus successfully synthesised on the gram to kilogram scales.
Optimization of the reaction using computer-simulated kinetics.