Open AccessFour stereoisomers of the novel μ‐opioid receptor agonist tapentadol hydrochloride
Author(s) -
Ravikumar Krishnan,
Sridhar Balasubramanian,
Pradhan Nitin,
Khunt Mayur
Publication year - 2011
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
eISSN - 1600-5759
pISSN - 0108-2701
DOI - 10.1107/s0108270111001727
Subject(s) - chemistry , monoclinic crystal system , chloride , crystal structure , hydrogen bond , hydrochloride , crystal (programming language) , crystallography , stereochemistry , medicinal chemistry , molecule , organic chemistry , computer science , programming language
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 P 2 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 P 2 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.