Preferred conformation of peptides based on cycloaliphatic C-alpha,alpha-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 (Ac(11)c), an alpha -amino acid conformationally constrained through a medium-ring C-i(alpha)<->C-i(alpha) cyclization, and either the L-Ala or Aib residue, along with the N-protected Ac(11)c 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 H-1-NMR techniques. Furthermore, the molecular structures of one derivative (Z-Ac(11)c-OH) and two peptides (the tripeptide ester Z-Aib-Ac(11)c-Aib-OtBu and the pentapeptide ester Z-Ac(11)c-(Aib)(2)-Ac(11)c-Aib-OtBu) have been determined in the crystal state by X-ray diffraction. The experimental results support the view that beta -bends and 3(10)-helices are preferentially adopted by peptides rich In Ac(11)c, the second largest cycloaliphatic C-alpha,C-alpha-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.