A chirally stable, atropoisomeric, C-alpha-tetrasubstituted alpha-amino acid: Incorporation into model peptides and conformational preference

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, i n combination with Ala, Gly, or Aib residues, was synthesized by solution m ethods and fully characterized. The solution conformational propensity of t hese peptides was determined by FT-IR absorption and H-1-NMR techniques. Mo reover, 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 t ogether, the results point to the conclusion that beta -bends and 3(10) hel ices are preferentially adopted by Bin-containing peptides, although the fu lly extended conformation would also be adopted in solution by the short ol igomers 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 inten se exciton-split Cotton effect of the B-1(b) binaphthyl transition near 225 nm.