Oxidation chemistry of the endogenous central nervous system alkaloid salsolinol-1-carboxylic acid.
The oxidation chemistry of salsolinol-1-carboxylic acid (1), an alkaloid endogenous to the central nervous system which is elevated as a result of ethanol consumption, has been studied by electrochemical approaches at pH 7.0 in aqueous solution. The first voltammetric oxidation peak of Ia of 1 at pH 7.0 occurs at Ep = +0.116 V, indicating that this alkaloid is a very easily oxidized compound. The peak Ia reaction is a 2e-2H+ oxidation of 1 to 1,2,3,4-tetrahydro-1-methyl-1-carboxy-6,7-isoquinolinedione (8), which rapidly decarboxylates (k > 10(3) s-1) to give predominantly the quinone methide tautomer of 3,4-dihydro-1-methyl-6,7-isoquinolinediol (2). The latter compound is responsible for the second observed oxidation peak IIa observed with 1. This peak is a 2e oxidation of 2 to a quinoid intermediate (9) which can either be attacked by water to yield 3,4-dihydro-1-methyl-5,7-dihydroxyisoquinolin-6-one (13b) (which is readily further oxidized to 3,4-dihydro-1-methyl-5-hydroxyisoquinoline-6,7-dione (3)) or aromatizes to yield 1-methyl-6,7-isoquinolinediol (4). Preliminary in vivo experiments have revealed that 2 and 13b are behavioral toxins when injected into the brains of laboratory mice. The in vitro oxidation reactions of 1 and 2 reported here might be of relevance to the neurodegenerative, behavioral, and addictive consequences of chronic alcoholism.
Zhang
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Department of Chemistry and Biochemistry, University of Oklahoma, Norman 73019.
Dryhurst
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004563:Electrochemistry; D000431:Ethanol / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction; D012490:Salsoline Alkaloids / Q000737:chemistry
D007546:Isoquinolines; D012490:Salsoline Alkaloids; D000431:Ethanol; C048152:1-carboxysalsolinol