A Chirally Stable, Atropoisomeric, C-Tetrasubstituted -Amino Acid: Incorporation into Model Peptides and Conformational Preference

Abstract

A variety of model peptides, including four complete homologous series, to the pentamer level, characterized by the recently proposed binaphthyl-based, axially chiral, Cα-tetrasubstituted, cyclic α-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 1H-NMR techniques. Moreover, the molecular structures of the free amino acid (S)-enantiomer and an Nα-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 β-bends and 310 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 1Bb binaphthyl transition near 225 nm.