Reinvestigation of the reactions of carbodiimides with alkoxycarbonylamino acid symmetrical anhydrides. Isolation of two N-acylureas.

J Izdebski, A Orłowska, R Anulewicz, E Witkowska, D Fiertek

Index: Int. J. Pept. Protein Res. 43 , 184, (1994)

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Abstract

Alkoxycarbonylamino acid symmetrical anhydrides were allowed to react with N,N'-diisopropylcarbodiimide. The determination of the decrease in carbodiimide concentration indicated that the reaction was slow and proceeded indirectly. It is presumed that symmetrical anhydride in the presence of basic carbodiimide is converted into oxazolone and alkoxycarbonylamino acid. The latter reacts with carbodiimide to give O-acylisourea which, in turn, rearranges to N-acylurea. A second minor product was found to be N-(N1,N2-bisalkoxycarbonyldipeptidyl)urea. The main pathway leading to the formation of this product starts with rearrangement of the symmetrical anhydride to N1,N2-bisalkoxycarbonyldipeptide acid. These experiments suggest that the reaction between anhydride and carbodiimide is not the source of N-acylurea in peptide synthesis.