Microwave irradiated high-speed solution synthesis of peptide acids employing Fmoc-amino acid pentafluorophenyl esters as coupling agents

Abstract

A high-speed solution phase synthesis of peptide acids employing commercially available Fmoc-amino acid pentafluorophenyl esters as coupling agents has been demonstrated. The coupling has been found to be fast and completed in 30-45 sec. A simple work-up of the reaction mixture has resulted <i>N</i>-protected peptide acids in good yield. Utilizing the present method, the coupling of difficult sequences containing highly hindered <img src='/image/spc_char/alpha.gif' border=0> , <img src='/image/spc_char/alpha.gif' border=0>-dialkyl amino acids has also been demonstrated. Further, the synthesis of diastereomeric dipeptides, Fmoc-Phg-Phe-OMe and Fmoc-D-Phg-Phe-OMe revealed that the coupling is free from racemization.