ELECTROCHEMICAL OXIDATION OF 6-HYDROXY-1,2,3,4-TETRAHYDRO-BETA-CARBOLINE IN AQUEOUS-SOLUTION

The electrochemical oxidation of 6-hydroxy-1,2,3,4-tetrahydro-beta-car boline (1), an alkaloid which occurs naturally in the mammalian brain, has been studied in aqueous solution particularly at physiological pH . The first voltammetric oxidation peak of 1 observed at the pyrolytic graphite electrode generates a radical intermediate which dimerizes t o give '-bi-(6-hydroxy-1,2,3,4-tetrahydro-beta-carboline) (3). However , the putative radical intermediate can also be further oxidized (1e) to give a C(5)-centered carbocation which can either dimerize in an io n-substrate reaction to give 3 or be attacked by water to give 5,6-dih ydroxy-1,2,3,4-tetrahydro-beta-carboline (8) which is rapidly oxidized fur-ther to 1,2,3,4-tetrahydro-beta-carboline-5,6-dione (9). In the p resence of glutathione dione 9 forms the 8-S-glutathionyl conjugate of 8 which is easily oxidized to the 8-S-glutathionyl conjugate of 9. It is suggested that 1 might be an alkaloid which is elevated in the bra in as a result of chronic alcoholism, and the roles of the oxidative t ransformations of this compound in some of the addictive and neurophat hological consequences of ethanol consumption are discussed.