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Independent synthesis of 5‐hydroxytryptamine‐4,7‐dione ‐ the neurocytotoxic product of autoxidation of 5,7‐dihydroxytryptamine
Author(s) -
Sinhababu Achintya K.,
Borchardt Ronald T.
Publication year - 1988
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570250422
Subject(s) - autoxidation , chemistry , benzaldehyde , hydrochloride , nitration , indole test , acetonitrile , organic chemistry , tris , ethanol , medicinal chemistry , catalysis , biochemistry
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.