Nitrone protecting groups for enantiopure N-hydroxyamino acids: synthesis of N-terminal peptide hydroxylamines for chemoselective ligations.
The synthesis of enantiopure N-benzylidene nitrones of N-hydroxy-alpha-amino acids and their incorporation using standard Fmoc-based peptide chemistry into solid-supported peptide chains is described. Deprotection and resin cleavage affords N-terminal peptide hydroxylamines, which are the key substrates for chemoselective ligations with C-terminal peptide alpha-ketoacids. This general route is applicable to a variety of different N-terminal residues and provides a general approach to the solid phase synthesis of peptide hydroxylamines.
Medina
S Irene
SI
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA19104, USA.
Wu
Jian
J
Bode
Jeffrey W
JW
D000596:Amino Acids / Q000737:chemistry*; D019811:Hydroxylamine / Q000737:chemistry*; D007202:Indicators and Reagents; D009589:Nitrogen Oxides / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D000596:Amino Acids; D007202:Indicators and Reagents; D009589:Nitrogen Oxides; D010455:Peptides; C015388:nitrones; D019811:Hydroxylamine