ELECTROCHEMICAL AND ENZYMATIC OXIDATION OF 5-HYDROXYTRYPTOPHAN

L-5-Hydroxytryptophan (5-HTPP) is the immediate precursor of the neurotransmitter 5-hydroxytryptamine (5-HT) in the central nervous system. Aberrant but unknown oxidized forms of 5-HTPP and 5-HT have been detected in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease. In order to provide some clues to the identities of the unknown oxidized forms of 5-HTPP in Alzheimer CSF, the electrochemically driven and enzyme-mediated (peroxidase + H2O2, ceruloplasmin + O2, tyrosinase + O2) oxidations of this indole have been studied. The key intermediate in these oxidation reactions, which appear to proceed by very similar chemical pathways, is proposed to be a C4-centered carbocation (2b) which reacts with available nucleophiles. Reaction of 2b with water ultimately leads to tryptophan-4,5-dione. Reaction of 2b with 5-HTPP (an ion-substrate dimerization) gives diastereomers of 5,5'-dihydroxy-4,4'-bi-tryptophan (A and B) and a further dimer (J) linked at the C4 position of one 5-HTPP residue and the C5-O position of the other. Carbocation 2b also attacks dimers A, B and J to give a family of trimeric compounds. Methods for the isolation of reaction products are described and spectral information supporting the proposed structures is given.