Synthesis and absolute configuration of optically pure enantiomers of a kappa-opioid receptor selective agonist.
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.
DeCosta
B
B
Section on Drug Design and Synthesis, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892.
George
C
C
Rothman
R B
RB
Jacobson
A E
AE
Rice
K C
KC
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
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