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 alpha-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.
Harwood
Laurence M
LM
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK. l.m.harwood@reading.ac.uk
Mountford
Simon J
SJ
Yan
Ran
R
D000577:Amides / Q000737:chemistry*; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D010081:Oxazolone / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
D000577:Amides; D009025:Morpholines; D010455:Peptides; D010081:Oxazolone