Geometry and Conformation of the α‐Aminoisobutyric Acid Residue in Simple Derivatives and Dipeptides. Four New X‐ray Structural Analyses and a Statistical Analysis from Known Crystal Data

Abstract

Abstract The results of X‐ray diffraction analyses on two α‐aminoisobutyric acid (Aib) derivatives, methyl α‐(acetylamino)isobutanoate (Ac‐Aib‐OMe, 1 ) and benzyl α‐[(benzyloxycarbonyl)amino]isobutanoate (Z‐Aib‐OBzl, 2 ), and two terminally blocked, Aib‐containing dipeptides, methyl α‐[(acetyl‐ L ‐alanyl)amino]isobutanoate (Ac‐ L ‐Ala‐Aib‐OMe, 3 ) and tert ‐butyl α‐{[(benzyloxycarbonyl)amino]isobutanoyl}‐ L ‐alaninate (Z‐Aib‐ L ‐Ala‐O t Bu, 4 ) are described. In the asymmetric unit of all four compounds two independent molecules were found. In all cases but one (molecule A of 3 ) the Aib residue is folded, the sets of Φ, ψ (or Φ, ψ T ) torsion angles falling in the region of the conformational energy map where both α‐ and 3 10 ‐helices are found. A correlating statistical analysis of bond lengths, bond angles, and torsion angles from available crystal structures of 20 Aib derivatives and 11 Aib‐containing linear dipeptides was also performed to obtain precise information on the geometry and conformation of the Aib residue without the influence of the constraints imposed by the intramolecular hydrogen bonds characterizing higher‐order folded and helical peptides.