Enzymatic O-methylation of the dopamine agonist dipropyl-5,6-dihydroxy-aminotetralin: isolation and structure elucidation of the O-methylated metabolite
- 24 Downloads
The (+)-enantiomer of the potent dopamine agonist dipropyl-5,6-dihydroxyaminotetralin (DP-5,6-diOH-ATN) is metabolizedin vitro by catechol-O-methyltransferase (comt) to oneO-methyl derivative. This compound was isolated from the incubation mixture by reversedphasehplc, after the incubation mixture had been purified over Sephadex G 10 columns and the excess parent catecholamine had been removed with alumina. One of the possibleO-methyl metabolites, dipropyl-5-hydroxy-6-methoxyaminotetralin, was synthesized from dipropyl-5,6-dimethoxyaminotetralin by a regioselective mono-demeth-ylation with iodotrimethylsilane. Comparison of Chromatographic and spectral data of the products from incubation and synthesis showed that different isomers are formed;i.e. DP-5,6-diOH-ATN is exclusively meta-O-methylated bycomtin vitro to dipropyl-5-methoxy-6-hydroxyaminotetralin.
KeywordsPublic Health Alumina Internal Medicine Dopamine Catecholamine
Unable to display preview. Download preview PDF.
- Gulliver, P.A. (1983)Biochem. Pharmacol. in press.Google Scholar
- Ho, T.L., and G.A.Olah (1977)Synthesis 417.Google Scholar
- Horn, A.S., D. Dijkstra, T.B.A. Mulder, H. Rollema andB.H.C. Westerink (1981)Eur. J. Med. Chem. 16, 469–472.Google Scholar
- Rollema, H., C.J. Grol andM.G.P. Feenstra (1982)Pharm. Weekbl. Sci. 4, 205 [Abstract].Google Scholar
- Westerink, B.H.C., andT.B.A. Mulder (1981)J. Neurochem. 35, 1449–1462.Google Scholar