Carbodiimide Method for Polypeptide Synthesis

The carbonimide compounds can be used in the condensation of amino and carboxyl groups. In this class of compounds, N'-DCC is relatively cheap and soluble in peptides to synthesize commonly used solvents. During the formation of peptide bonds, carbodiylamine is converted to the corresponding urea derivatives, and N, nd-dicyclohexyl urea can be precipitated from the reaction fluid. It is obvious that the ammonia solution and hydrolysis rate of the active intermediate are different from the activation of carbon diylamine, so that the peptide synthesis can be carried out in the water-bearing medium. 

By several groups' study, mechanism of peptide condensation reaction has been established, based on carbodiimide as condensating agent. Carbon carboxylic acid ions are added to protonated carbodiimide and then form highly reactive O - acyl urea; Although this intermediate has not been isolated, it is deduced from very similar stable compounds. O- acyl urea reacts with amino components to produce protected peptides and urea derivatives. Or, it is in equilibrium with the protonised form of o-acyl isourea, and the second carboxylate nucleophilic attack produces symmetrical amino anhydride, N and N - disubstituted urea. 

The former and amino acid's reaction gets peptide derivatives and free amino acids. In the case of base catalysis, the subreaction of DCC is used to transfer the acyl from the isocarbamide atom to the nitrogen atom, producing N- acyl urea 71, which no longer has any further ammonia solution. Not only it is the excessive alkali catalyzed by the oyl transfer of o-n, but also the alkaline amino component or carbon diylamine can catalyze the side reaction.

In addition, the polar solvent is beneficial to this reaction.