Simple and Mild One-Pot Synthesis of Dipeptidyl Ureas via Carbamoyl Azides of α-N-Protected Amino Acids

Abstract

A simple and mild one-pot synthesis of potentially bioactive α-N-protected dipeptidyl ureas is reported. The procedure involves the reaction between the carbamoyl azide of an α-N-protected amino acid and an α-amino acid methyl ester. The reaction is fast (3 h at 45 °C), regardless of the nature of both the reagents, and racemization free. The reported protocol represents a valid alternative to existing methods.

Keywords:

• Amino acid methyl esters
• amino acids
• carbamoyl azide
• Curtius rearrangement
• dipeptidyl ureas

ACKNOWLEDGMENTS

The authors are grateful to Dr. S. Turco for recording ¹H and ¹³C NMR spectra, Dr. I. Duse for MS measurements, and Mr. P. Padovani for expert instrumental maintenance.