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

The (+)-enantiomer of the potent dopamine agonist dipropyl-5,6-dihydroxyaminotetralin (DP-5,6-diOH-ATN) is metabolized in vitro by catechol-O-methyltransferase (COMT) to one O-methyl derivative. This compound was isolated from the incubation mixture by reversed-phase HPLC, 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 possible O-methyl metabolites, dipropyl-5-hydroxy-6-methoxyaminotetralin, was synthesized from dipropyl-5,6-dimethoxyaminotetralin by a regioselective mono-demethylation 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 by COMT in vitro to dipropyl-5-methoxy-6-hydroxyaminotetralin.