title: Four stereoisomers of the novel μ-opioid receptor agonist tapentadol hydrochloride.
abstract: The crystal and molecular structures of four stereoisomers of tapentadol hydrochloride [systematic name: 3-(3-hydroxyphenyl)-N,N,2-trimethylpentan-1-aminium chloride], C(14)H(24)NO(+)·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 P2(1), each with two tapentadol cations and two chloride anions in the asymmetric unit, while stereoisomers (III) and (IV) crystallize in the orthorhombic space group P2(1)2(1)2(1), with one tapentadol cation and one chloride anion in the asymmetric unit. The absolute configurations of the four enantiomers 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 aminopropyl 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 tapentadol molecules, resulting in one-dimensional helical chains in the crystal packing in each case.
authors.affiliation: Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad, India. sshiya@yahoo.com
authors.forename: Krishnan
authors.initials: K
authors.lastname: Ravikumar
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Sridhar
authors.forename: Nitin
authors.initials: N
authors.lastname: Pradhan
authors.forename: Mayur
authors.initials: M
authors.lastname: Khunt
mesh_terms: D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013237:Stereoisomerism; D000077432:Tapentadol
chemical_list: D010636:Phenols; D017450:Receptors, Opioid, mu; D000077432:Tapentadol