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 (4 R )‐ and (4 S )‐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.
Bhowal et al. (Wed,) studied this question.