Novel chiral cyrene-derived Cyr residues were incorporated into peptides. The α,α-disubstituted amino acid residue was introduced using the Ugi reaction. X-ray crystallographic analysis of R– and S-Cyr residues indicated preference to adopt left- and right-handed α-helical conformations, respectively. Propensity to adopt positions in β- and γ-turn hydrogen-bonded conformers was also indicated in the solid state and by NMR studies in solution, highlighting potential in peptide design and conformational control.
ABSTRACT
Cyrene-derived α,α-disubstituted amino acids (H-Cyr-OH) are introduced into peptides using the multiple component Ugi reaction. Conformational analysis of the Cyr monomer and dimer was performed by X-ray crystallography and NMR spectroscopy. In the solid state, the backbone torsion angle values of (4R)- and (4S)-Cyr were respectively characteristic of left- and right-handed α-helical conformers; however, the dimer appeared to adopt a 10-membered hydrogen bond in a distorted type III β-turn. In solution, solvent shielded amide NH hydrogens suggested that the Cyr residue could adopt the central position of γ-turn conformations. With conformational properties indicative of α-, β-, and γ-turns, the Cyr residue offers interesting potential as a novel chiral α,α-disubstituted amino acid for exploring chemical space.
