Oxidation Chemistry of 5-Hydroxytryptamine. 1. Mechanism and Products Formed at Micromolar Concentrations

Article abstract of DOI:10.1021/jo00389a032

The oxidation of very low concentrations (<30 μM) of 5-hydroxytryptamine (1) in 0.01 M HCl has been studied by using electrochemical and other analytical techniques.The initial oxidation is a 1e, 1H⁺ reaction, giving a phenoxyl radical which exists in equilibrium with aryl, C(4)^., and N(1)^. radicals.At low potentials the latter radicals can react to give dimeric products.At higher potentials, however, the primary phenoxyl radical is further oxidized (1e,1H⁺) to a reactive quinone imine.The quinone imine is rapidly attacked by water to give 4,5-dihydroxytryptamine (7), which is further oxidized to tryptamine-4,5-dione (B).In aqueous solution at pH 2 B is slowly attacked by water to give 4,5,7-trihydroxytryptamine, which is further oxidized (2e,2H⁺) to 5-hydroxytryptamine-4,7-dione (11).Compounds B and 11 then react together to give a hydroxylated tryptamine dimer.The facile oxidation of 1 give at least two neurotoxins, 7 and 9, might provide insight into the previously proposed anomolous oxidative metabolism of 1 as an underlying cause of various mental disorders.