409320-11-2Relevant articles and documents
Role of secondary structure in the asymmetric acylation reaction catalyzed by peptides based on chiral Cα-tetrasubstituted α-amino acids
Formaggio, Fernando,Barazza, Alessandra,Bertocco, Andrea,Toniolo, Claudio,Broxterman, Quirinus B.,Kaptein, Bernard,Brasola, Elena,Pengo, Paolo,Pasquato, Lucia,Scrimin, Paolo
, p. 3849 - 3856 (2007/10/03)
In a recent series of papers, Miller and co-workers were able to show that His(π-Me)-based, terminally protected peptides are potent catalysts of the asymmetric acyl transfer reaction, useful for the kinetic resolution of alcohols. In a structure-supporting solvent, one of the most active compounds, an Aib-containing tetrapeptide, is folded in a doubly intramolecularly H-bonded β-hairpin motif incorporating a type-II′ β-turn conformation. In this work, we have expanded the study of the Miller tetrapeptide by examining a set of analogues and shorter sequences (dipeptide amides), characterized by chiral Cα-tetrasubstituted α-amino acids of diverging bulkiness and optical configuration. Peptide synthesis in solution, conformational analysis by FT-IR absorption and 1H NMR techniques, and screening of catalytic activity as well have been performed. Our results confirm the close relationship between the β-hairpin 3D-structure and the catalytic activity of the peptides. A tetrapeptide analogue slightly more selective than the Miller compound has been found. However, the terminally protected, industrially more appealing, dipeptide amides are poorly effective.
Nitroxyl peptides as catalysts of enantioselective oxidations
Formaggio, Fernando,Bonchio, Marcella,Crisma, Marco,Peggion, Cristina,Mezzato, Stefano,Polese, Alessandra,Barazza, Alessandra,Antonello, Sabrina,Maran, Flavio,Broxterman, Quirinus B.,Kaptein, Bernard,Kamphuis, Johan,Vitale, Rosa Maria,Saviano, Michele,Benedetti, Ettore,Toniolo, Claudio
, p. 84 - 93 (2007/10/03)
The achiral, nitroxyl-containing α-amino acid TOAC (TOAC = 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), in combination with the chiral α-amino acid Cα-methyl valine [(αMe)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 Nα-acylated dipeptide alkylamide with the -TOAC-(αMe)Val- sequence folded in a stable, intramolecularly hydrogen-bonded β-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(αMe)Val-NHiPr, based on the X-ray diffraction structure of the latter.
