Resolution and absolute stereochemistry of 6,7-dimethoxy-4-phenyl- 1,2,3,4-tetrahydroisoquinoline. The crystal structure of the R-hydrochloride salt form.
Stereospecific multistep synthesis and resolution of 6,7-dimethoxy-4- phenyl-1,2,3,4-tetrahydroisoquinoline (3) has been achieved from its racemic base. The absolute configurations of the optical antipodes converted into their hydrochloride salt forms have been determined by X-ray diffractometric analysis, thus permitting assignment of the antipodes as the (+)-(4R)-3 and (-)-(4S)-3 enantiomers. The crystal structures of the two enantiomers are related as mirror images and only the (4R)-3.HCl form has been fully determined by three-dimensional X-ray diffraction. In the solid state, the carbon atoms of the two methoxy groups deviate slightly from the benzene-ring plane and the chirally oriented phenyl substituent is almost perpendicularly tilted out of conjugation with the isoquinoline system. Examination of the enantiomers in several biochemical tests for 5-HT, NE and DA uptake inhibition-activity revealed an exclusive preference for the (4S)-enantiomer. These results are in accord with previous suggestions that the S-configurational state of the 4-phenyl substituent is important for biological activity.
Mondeshka
D
D
Institute of Chemical Technology, Sofia, Bulgaria.
Angelova
I
I
Stensland
B
B
Werner
P E
PE
Ivanov
C
C
D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D007546:Isoquinolines / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines; D014961:X-Ray Diffraction
D000929:Antidepressive Agents, Tricyclic; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C031333:1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline