DIRECT OBSERVATION OF THE REACTION OF THE QUINONE-METHIDE FROM 5,6-DIHYDROXYINDOLE WITH THE NUCLEOPHILIC AZIDE ION

Investigation of the oxidation of melanagenic intermediates and, in particular, the ultimate oxidative polymerisation of 5,6-dihydroxyindole (1) is important for a comprehensive understanding of the biosynthesis of melanin. Oxidation of 1 leads to the formation of its corresponding quinone methide, a reactive intermediate. We report a novel approach using a fast reaction technique to produce the quinone methide of 1 in situ and study its chemistry. In aqueous solution at pH 9, the quinone methide has a lifetime of < 0.1 s due to interaction with the solvent. As an example of the chemistry of the quinone methide of 1, it was demonstrated that it interacts with the nucleophilic azide ion. From comparison with the corresponding reactions of the quinone-methide from 5-methoxy-6-hydroxyindole (2), it is inferred that the indoloquinone of 1 is involved in the pathways to melanin formation. The importance of the involvement of the quinone methide of 1 in the pathway to melanin formation is in contrast to the pathway involving dimer products arising from 1.