Four stereoisomers of the novel -opioid receptor agonist tapenta-dol hydro-chloride

Abstract

The crystal and mol-ecular structures of four stereoisomers of tapenta-dol hydro-chloride [systematic name: 3-(3-hy-droxy-phenyl)-N,N,2-trimethyl-pentan-1- aminium chloride], C14H24NO+·Cl -, a novel analgesic agent, have been determined by X-ray crystal structure analysis. Resolution of the isomers was carried out by reverse-phase and chiral high-performance liquid chromatographic (HPLC) methods. Stereoisomers (I) and (II) crystallize in the monoclinic space group P21, each with two tapenta-dol cations and two chloride anions in the asymmetric unit, while stereoisomers (III) and (IV) crystallize in the ortho-rhom-bic space group P212121, with one tapenta-dol cation and one chloride anion in the asymmetric unit. The absolute configurations of the four enantio-mers were determined unambiguously by X-ray crystallography. The crystal structures reveal the stereochemistries at the 3-ethyl and 2-methyl groups to be R,R, S,S, S,R and R,S in stereoisomers (I)-(IV), respectively. The ethyl and amino-propyl groups adopt different orientations with respect to the phenol ring for (I) and (IV). In all four structures, the chloride ions take part in N - H⋯Cl and O - H⋯Cl hydrogen bonds with the tapenta-dol mol-ecules, resulting in one-dimensional helical chains in the crystal packing in each case. © 2011 International Union of Crystallography.