ELECTROCHEMICAL AND ENZYMATIC OXIDATION OF 5-HYDROXYTRYPTOPHOL .2. STUDIES AT PHYSIOLOGICAL PH

The key event in the electrochemical oxidation of 5-hydroxytryptophol (5-HTOL) at physiological pH is formation of a carbocation intermediate (15b). This intermediate undergoes a series of ion-substrate coupling reactions. The major product of these reactions is 5,5-dihydroxy-4,4'-bitryptophol (A). Further attack of carbocation 15b on A yields several trimers including one containing an ether bridge between two 5-HTOL residues (I). This key trimer is the precursor of a number of dioxepin derivatives. Carbocation 15b can also be attacked by water yielding, ultimately, tryptophol-4,5-dione (B). Overall, electro-oxidation of 5-HTOL generates a very complex mixture of products. Peroxidase/H2O2, ceruloplasmin/O2, and tyrosinase/O2 also oxidize 5-HTOL. The product profiles generated in these enzyme-mediated reactions are very similar to the electrochemically driven process. The possibility is discussed that oxidation chemistry or biochemistry of 5-HTOL or other biogenic indoles in the central nervous system might play a role in the etiology of neurodgenerative illnesses.