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

The molecular and crystal structures of the C-alpha,alpha-dialkylated alpha-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 alpha- and beta-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(alpha (phi) and C(alpha)-C' (psi) bonds for the single Ac3c residue of Piv-Ac3c-OH, the alpha- and beta-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 phi,psi 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-alpha-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 (alpha-form)] or the cis amide conformations [t-Boc-Ac3c-OH (beta-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 alpha-amino acid are zwitterionic.