title: Synthesis and absolute configuration of optically pure enantiomers of a kappa-opioid receptor selective agonist.
abstract: The enantiomers of U50,488, ligands highly selective for kappa-opioid receptors, have been prepared by a refined procedure and their optical purity demonstrated. The absolute configuration of (+)-trans-2-pyrrolidinyl-N-methylcyclohexylamine, a chemically versatile intermediate for synthesis of analogs of kappa-opioid receptor ligands with defined chirality, has been determined to be 1S,2S by X-ray crystallographic analysis. This intermediate has been used to synthesize the optically pure U50,488 enantiomers with known absolute configuration.
authors.affiliation: Section on Drug Design and Synthesis, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892.
authors.forename: B
authors.initials: B
authors.lastname: DeCosta
authors.forename: C
authors.initials: C
authors.lastname: George
authors.forename: R B
authors.initials: RB
authors.lastname: Rothman
authors.forename: A E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: K C
authors.initials: KC
authors.lastname: Rice
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D008024:Ligands; D011759:Pyrrolidines / Q000138:chemical synthesis*; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D008024:Ligands; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer