Role of secondary structure in the asymmetric acylation reaction catalyzed by peptides based on chiral C alpha-tetrasubstituted alpha-amino acids.
In a recent series of papers, Miller and co-workers were able to show that His(pi-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 beta-hairpin motif incorporating a type-II' beta-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 C(alpha)-tetrasubstituted alpha-amino acids of diverging bulkiness and optical configuration. Peptide synthesis in solution, conformational analysis by FT-IR absorption and (1)H NMR techniques, and screening of catalytic activity as well have been performed. Our results confirm the close relationship between the beta-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.
Formaggio
Fernando
F
Department of Chemistry, University of Padova, and ICB, CNR, 35131 Padua, Italy.
Barazza
Alessandra
A
Bertocco
Andrea
A
Toniolo
Claudio
C
Broxterman
Quirinus B
QB
Kaptein
Bernard
B
Brasola
Elena
E
Pengo
Paolo
P
Pasquato
Lucia
L
Scrimin
Paolo
P
D000215:Acylation; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D000596:Amino Acids; D010455:Peptides; D012996:Solutions