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Enzymatic O-methylation of the dopamine agonist dipropyl-5,6-dihydroxy-aminotetralin: isolation and structure elucidation of the O-methylated metabolite

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Abstract

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 bycomt in vitro to dipropyl-5-methoxy-6-hydroxyaminotetralin.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Laboratory of Pharmaceutical and Analytical Chemistry, State University of Groningen, Antonius Deusinglaan 2, 9713, AW Groningen, The Netherlands

    H. Rollema & C. J. Grol

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  1. H. Rollema
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  2. C. J. Grol
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In honour of Professor Faber on the occasion of his 25-years' professorate.

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Rollema, H., Grol, C.J. Enzymatic O-methylation of the dopamine agonist dipropyl-5,6-dihydroxy-aminotetralin: isolation and structure elucidation of the O-methylated metabolite. Pharmaceutisch Weekblad Scientific Edition 5, 159–164 (1983). https://doi.org/10.1007/BF01961474

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