Morpholinone mediated oxazolone‐free C ‐terminus amide coupling permitting a convergent strategy for peptide synthesis

3‐Substituted‐5‐phenylmorpholinones have been demonstrated to act as N ‐protected C ‐terminus activated α‐amino acids capable of undergoing solution phase N ‐terminus peptide extension following standard coupling procedures. The N ‐acylated morpholinones do not undergo epimerisation of the stereocentre of the C ‐terminus amino acid residue as oxazolone formation is sterically prevented, although C ‐terminus peptide coupling is still possible. This convergent approach to peptide synthesis is exemplified by the preparation of L‐ala‐L‐ala‐L‐ala and L‐ala‐D‐ala‐L‐ala. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.