Synthesis and Hydrogen Bonding Capabilities of Biphenyl-Based Amino Acids Designed To Nucleate β-Sheet Structure

• Published in: Journal of organic chemistry Vol. 61; no. 9; pp. 3127 - 3137
• Main Authors: Nesloney, Carey L, Kelly, Jeffery W
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.05.1996; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; COMPLETE SEQUENCE; FOLDING PATTERN; SOMATOSTATIN; DIRECTED ORTHO-METALATION; TEMPERATURE-DEPENDENT CHANGES; LINEAR PEPTIDES; CONFORMATION; MODEL PEPTIDES; POLYPEPTIDES; WATER
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo952194k

The syntheses of 3‘-(aminoethyl)-2-biphenylpropionic acid (1) and 2-amino-3‘-biphenylcarboxylic acid (2) are described. These residues were designed to nucleate β-sheet structure in aqueous solution when incorporated into small, amphiphilic peptides in place of the backbone of the i + 1 and i + 2 residues of the β-turn. N-Benzyl-3‘-(2-(benzylamido)ethyl)-2-biphenylpropamide (3) and N-benzyl-(2-benzylamido)-3‘-biphenylamide (4) were synthesized and studied as model compounds to investigate the hydrogen-bonding capabilities of residues 1 and 2, respectively. The X-ray crystal structure of 3 indicates that a 13-membered intramolecular hydrogen-bonded ring is formed, while the remaining amide proton and carbonyl are involved in intermolecular hydrogen bonding. Infrared and variable-temperature NMR experiments indicate that, in solution (CH2Cl2), 3 exists as an equilibrium mixture of the 13- and the 15-membered intramolecularly hydrogen-bonded conformers with the 15-membered ring conformer being favored. Amide 4 was shown to exist in solution (CH2Cl2) as an equilibrium mixture of the 11-membered intramolecular hydrogen-bonded ring and a nonbonded conformation. No contribution from the 9-membered hydrogen-bonded ring conformation was observed. The X-ray crystal structure of 4 indicated the absence of intramolecular hydrogen bonding in the solid state.