Quantitative description of epimerization pathways using the carbodiimide method in the synthesis of peptides

Abstract

The mechanism of epimerization in carbodiimide synthesis has been investigated by varying the side chain of the activated acids. A series of peptides N-benzyloxycarbonyl-Ala-Xaa-OH with 20 different residues Xaa were coupled with valine methyl ester in dichloromethane and dimethylformamide. The kinetic data and the extent of epimerization were determined for the peptide synthesis and the aminolysis of isolated oxazol-5(4H)-ones by means of IR spectroscopy, polarimetry and reversed-phase HPLC. Combining the results we succeeded for the first time in a quantitative description of the overlapping pathways of epimerization and their dependence on amino acid sequence during carbodiimide synthesis.