Nitroxyl peptides as catalysts of enantioselective oxidations.
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.
Formaggio
Fernando
F
Department of Organic Chemistry, University of Padova, CNR Centre CSB, Italy.
Bonchio
Marcella
M
Crisma
Marco
M
Peggion
Cristina
C
Mezzato
Stefano
S
Polese
Alessandra
A
Barazza
Alessandra
A
Antonello
Sabrina
S
Maran
Flavio
F
Broxterman
Quirinus B
QB
Kaptein
Bernard
B
Kamphuis
Johan
J
Vitale
Rosa Maria
RM
Saviano
Michele
M
Benedetti
Ettore
E
Toniolo
Claudio
C
D000098:Acetophenones / Q000737:chemistry; D000598:Amino Acids, Cyclic / Q000737:chemistry; D000621:Aminoisobutyric Acids / Q000737:chemistry; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010626:Phenylethyl Alcohol / Q000737:chemistry; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013113:Spin Labels; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives / Q000737:chemistry*; D014961:X-Ray Diffraction
D000098:Acetophenones; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids; C448019:C(alpha)-methyl valine; D003497:Cyclic N-Oxides; D003509:Cyclohexanecarboxylic Acids; D009589:Nitrogen Oxides; D009842:Oligopeptides; D013113:Spin Labels; C014966:1-aminocyclohexanecarboxylic acid; C039900:nitroxyl; D014633:Valine; D010626:Phenylethyl Alcohol; C038699:acetophenone; C037109:2,2,6,6-tetramethylpiperidine-N-oxide-4-amino-4-carboxylic acid