Independent synthesis of 5-hydroxytryptamine-4,7-dione - the neurocytotoxic product of autoxidation of 5,7-dihydroxytryptamine

Synthesis of 5-hydroxytryptamine-4,7-dione hydrochloride ( 20 ) is described starting from 3-bromo-4,5-dimethoxybenzaldehyde ( 6 ). Compound 6 was converted to 2,3,5-tris(benzyloxy)benzaldehyde ( 10 ) in 4 steps. Nitromethylenation of 10 followed by nitration and subsequent reductive cyclization gave 4,5,7-tris(benzyloxy)indole ( 13 ). Introduction of the aminoethyl (hydrochloride) side chain on C-3 of 13 , via the corresponding indole-3-acetonitrile, and subsequent debenzylation generated in situ, 4,5,7-trihydroxytryptamine hydrochloride ( 19 ) which underwent rapid autoxidation in ethanol to give 20 . 4,5,7-Trihydroxyindole ( 21 ) and 3-2-(ethoxycarbonylamino)ethyl]-4,5,7-trihydroxyindole ( 24 ), both generated in situ, were also found to undergo rapid autoxidation to the corresponding 5-hydroxyindole-4,7-diones.