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1 H ‐Azepine‐4‐amino‐4‐carboxylic Acid: A New α,α‐Disubstituted Ornithine Analogue Capable of Inducing Helix Conformations in Short Ala‐Aib Pentapeptides
Author(s) -
Pellegrino Sara,
Contini Alessandro,
Clerici Francesca,
Gori Alessandro,
Nava Donatella,
Gelmi Maria Luisa
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201104023
Subject(s) - chemistry , azepine , pentapeptide repeat , stereochemistry , carboxylic acid , yield (engineering) , amino acid , enantiomer , ornithine , peptide , arginine , biochemistry , materials science , metallurgy
Abstract A very efficient synthesis of orthogonally protected 1 H ‐azepine‐4‐amino‐4‐carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1‐amino‐4‐oxo‐cyclohexane‐4‐carboxylic acid. Both enantiomers were used for the preparation of pentapeptide models containing Ala, Aib, and Azn. Conformational studies using both spectroscopic techniques (NMR, CD) and molecular dynamics on model 5‐mer peptides showed that the ( R )‐Azn isomer possesses a marked helicogenic effect.