Preferred conformation of peptides based on cycloalipathic C(α,α)-disubstituted glycines: 1-Amino-cycloundecane-1-carboxylic acid (Ac11c)

Two complete series of N-protected oligopeptide esters to the pentamer level from 1-amino-cycloundecane-1-carboxylic acid (AC11c), an α-amino acid conformationally constrained through a medium-ring C(i)(α)-C(i)(α) cyclization, and either the L-Ala or Aib residue, along with the N-protected Ac11c monomer and homo-dimer alkylamides, have been synthesized by solution methods and fully characterized. The preferred conformation of these model peptides has been assessed in deuterochloroform solution by FT-IR absorption and 1H-NMR techniques. Furthermore, the molecular structures of one derivative (Z-Ac11c-OH) and two peptides (the tripeptide ester Z-Aib-Ac11c-Aib-OtBu and the pentapeptide ester Z-Ac11c-(Aib)2-Ac11c-Aib-OtBu) have been determined in the crystal state by X-ray diffraction. The experimental results support the view that β-bends and 310-helices are preferentially adopted by peptides rich in Ac11c, the second largest cycloaliphatic C(α,α)-disubstituted glycine known. This investigation has allowed the authors to approach the completion of a detailed conformational analysis of the whole 1-amino-cycloalkane-1-carboxylic acid (Ac(n)c, with n = 3-12) series, which represents the prerequisite for their recent proposal of the 'Ac(n)c scan' concept. Copyright (C) 2000 European Peptide Society and John Wiley and Sons, Ltd