A chirally stable, atropoisomeric, C-alpha-tetrasubstitued alpha-amino acid: incorporation into model peptides and conformational preferences

A variety of model peptides, including four complete homologous series, to the pentamer level. characterized by the recently proposed binaphthyl-based, axially chiral, C-alpha-tetrasubstituted, cyclic alpha -amino acid Bin, in combination with Ala, Gly, or Aib residues, was synthesized by solution methods and fully characterized. The solution conformational propensity of these peptides was determined by FT-IR absorption and H-1-NMR techniques. Moreover, the molecular structures of the free amino acid (S)-enantiomer and an N-alpha-acylated dipeptide alkylamide with the heterochiral sequence -(R)-Bin-Phe- were assessed in the crystal state by X-ray diffraction. Taken together, the results point to the conclusion that beta -bends and 3(10) helices are preferentially adopted by Bin-containing peptides, although the fully extended conformation would also be adopted in solution by the short oligomers to some extent. We also confirmed the tendency of (R)-Bin to fold a peptide chain into right-handed bend and helical structures. The absolute configuration of the Bin residue(s) was correlated with the typically intense exciton-split Cotton effect of the B-1(b) binaphthyl transition near 225 nm.