Nitroxyl peptides as catalysts of enantioselective oxidations

Chemistry. 2002 Jan 4;8(1):84-93. doi: 10.1002/1521-3765(20020104)8:1<84::aid-chem84>3.0.co;2-n.

Abstract

The achiral, nitroxyl-containing alpha-amino acid TOAC (TOAC = 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), in combination with the chiral alpha-amino acid C(alpha)-methyl valine [(alphaMe)Val], was used to prepare short peptides (from di- to hexa-) that induced the enantioselective oxidation of racemic 1-phenylethanol to acetophenone. The best catalyst was an N(alpha)-acylated dipeptide alkylamide with the -TOAC-(alphaMe)Val- sequence folded in a stable, intramolecularly hydrogen-bonded beta-turn conformation with large, lipophilic (hydrophobic) N- and C-terminal blocking groups. We rationalized our findings by proposing models for the diastereomeric intermediates between (R)-[and (S)]-1-phenylethanol and the catalyst Fmoc-TOAC-L-(alphaMe)Val-NHiPr, based on the X-ray diffraction structure of the latter.

MeSH terms

  • Acetophenones / chemistry
  • Amino Acids, Cyclic / chemistry
  • Aminoisobutyric Acids / chemistry
  • Catalysis
  • Chemical Phenomena
  • Chemistry, Physical
  • Cyclic N-Oxides / chemical synthesis*
  • Cyclic N-Oxides / chemistry
  • Cyclohexanecarboxylic Acids / chemistry
  • Models, Molecular
  • Molecular Structure
  • Nitrogen Oxides / chemistry*
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oxidation-Reduction
  • Phenylethyl Alcohol / chemistry
  • Protein Conformation
  • Spectrophotometry, Infrared
  • Spectroscopy, Fourier Transform Infrared
  • Spin Labels
  • Stereoisomerism
  • Valine / analogs & derivatives
  • Valine / chemistry*
  • X-Ray Diffraction

Substances

  • Acetophenones
  • Amino Acids, Cyclic
  • Aminoisobutyric Acids
  • C(alpha)-methyl valine
  • Cyclic N-Oxides
  • Cyclohexanecarboxylic Acids
  • Nitrogen Oxides
  • Oligopeptides
  • Spin Labels
  • 1-aminocyclohexanecarboxylic acid
  • nitroxyl
  • Valine
  • Phenylethyl Alcohol
  • acetophenone
  • 2,2,6,6-tetramethylpiperidine-N-oxide-4-amino-4-carboxylic acid