Comparative study of methods to couple hindered peptides.
A comparative study of modern coupling reactions involving Boc-protected amino acid derivatives and dipeptides with N-terminal alpha,alpha-dialkylation and N-methylation was carried out. The coupling reactions were run using either equimolar amounts of the amino and activated carboxyl components or an excess of the activated carboxyl component. Yields of the target tripeptide Boc-Phe-Xaa-Phe-OBzl (Xaa = (NMe)Ala, (NMe)Aib, or (NMe) alpha Ac5c) were compared. Less than 10% of the product was obtained from methods utilizing pivaloyl mixed anhydride, pentafluorophenyl ester or acyl fluoride activation when Xaa = (NMe)Aib and (NMe) alpha Ac5c. At room temperature, significant yields of these two products were obtained from reactions which utilized an excess of the HBTU reagent (O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate), the PyBroP reagent (bromo-tris-pyrrolidino-phosphonium hexafluorophosphate) or Boc-Phe-NCA (Boc-protected phenylalanine N-carboxyanhydride). Moreover, the Boc-Phe-NCA method was superior when used over a prolonged reaction time or at elevated temperature.
Spencer
J R
JR
Department of Chemistry, University of California San Diego, La Jolla.
Antonenko
V V
VV
Delaet
N G
NG
Goodman
M
M
D000595:Amino Acid Sequence; D004151:Dipeptides / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry*; D008722:Methods; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis
D004151:Dipeptides; D007202:Indicators and Reagents; D009842:Oligopeptides