Conformations of β-amino acid residues in peptides: X-ray diffraction studies of peptides containing the achiral residue 1-aminocyclohexaneacetic acid, β^3,3Ac₆c

Abstract

The conformational preferences of the 3,3-disubstituted β-amino acid residue, 1-aminocyclohexaneacetic acid (β^3,3Ac₆c) have been investigated by determining the crystal structures of the parent amino acid, the hydrochloride derivative, 10 protected derivatives and di and tripeptides. The symmetrical cyclohexyl substituent at the β -position restricts the values of the torsion angles Φ(N-Cβ) and θ(Cβ-C^α) to approximately gauche values (±60°). Relatively few intramolecularly hydrogen bonded conformations are observed. In the dipeptide Boc-β^3,3Ac₆c-β^3,3Ac₆c-NHMe a C₆ hydrogen bond is observed. In Piv-Pro-β^3,3Ac₆c-NHMe a C₁₁ hydrogen bonded hybrid turn is characterized. In a majority of cases the amino group occupies the axial position in the cyclohexane ring. The conformations observed are compared with crystallographically observed structures for other β-residues, including β^2,2Ac₆c.