Resolution, absolute stereochemistry, and enantioselectivity of 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol.
Racemic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) was found to be an effective potentiator of the contractile response of norepinephrine (NE) on rat anococcygeus muscle. This paper describes the resolution of racemic PI-OH by an HPLC method to give the optically pure enantiomers (+)-1 and (-)-1. The absolute configuration of (+)-1 was R as determined by CD analysis and by single-crystal X-ray diffractometric analysis of the methiodide 6 derived from (+)-1. Examination of the effects of the enantiomers to potentiate the contraction of the rat anococcygeus muscle by NE showed a high degree of enantioselectivity. The NE potentiation was found to reside exclusively in (R)-(+)-1; the activity ratio being 21 at 3 x 10(-6) M, whereas (S)-(-)-1 did not show any potentiating and inhibiting activity.
Kihara
M
M
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Kashimoto
M
M
Kobayashi
S
S
Ishida
Y
Y
Moritoki
H
H
Taira
Z
Z
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004357:Drug Synergism; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009627:Nomifensine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D014961:X-Ray Diffraction
C056761:4-hydroxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; D009627:Nomifensine; D009638:Norepinephrine