Crystallographic characterization of conformation of 1-aminocyclopropane-1-carboxylic acid residue (Ac3c) in simple derivatives and peptides*

The molecular and crystal structures of the C^α,α-dialkylated α-amino acid residue 1-aminocyclopropane-1-carboxylic acid hemihydrate (H₂^⊕-Ac₃c-O^?·½ H₂O) and nine derivatives and dipeptides have been determined by X-ray diffraction. The derivatives are pBrBz-Ac₃c-OH, Piv-Ac₃c-OH, Z-Ac₃c-OH, the α- and β-forms of t-Boc-Ac₃c-OH, Z-Ac₃c-OMe, and the 5(4H)-oxazolone from pBrBz-Ac₃c-OH; the dipeptides are H-(Ac₃c)₂-OMe and c(Ac₃c)₂. The values determined for the torsion angles about the N-C^α (φ) and C^α-C′ (φ) bonds for the single Ac₃c residue of Piv-Ac₃c-OH, the α- and β-forms of t-Boc-Ac₃-OH and Z-Ac₃c-OMe, and the C-terminal Ac₃c residue of H-(Ac₃c)₂-OMe correspond to folded conformations in the “bridge” region of the Ramachandran map. The structures of pBrBz-Ac₃c-OH and Z-Ac₃c-OH, however, are unusual in having a semi-extended conformation for the φ,ψ angles. The N-terminal Ac₃c residue of H-(Ac₃c)₂-OMe adopts a novel type of C₅ conformation, characterized inter alia by an (amino) N ? H-N (peptide) intramolecular hydrogen bond. While the acyl N^α-blocking groups form trans amides (pBrBz-Ac₃c-OH and Piv-Ac₃c-OH), the urethane groups may adopt either the trans Z-Ac₃c-OH and t-Boc-Ac₃c-OH(α-form)] or the cis amide conformations t-Boc-Ac₃c-OH(β-form) and Z-Ac₃c-OMe]. The five- and six-membered rings of the 5(4H)-oxazolone and the 2,5-dioxopiperazine, respectively, are planar. The four independent molecules in the asymmetric unit of the free α-amino acid are zwitterionic.