Atropoisomeric melanin intermediates by oxidation of the melanogenic precursor 5,6-dihydroxyindole-2-carboxylic acid under biomimetic conditions

A great part of the current knowledge about the chemistry and the structure of melanins arises from in vitro studies involving oxidative polymerization of 5,6-dihydroxyindoles under biomimetic conditions. Previous studies carried out on the 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a key intermediate in the biosynthesis of the dark brown eumelanins, had delineated a reaction pathway involving mainly the formation of the symmetric dimer 4-4′-biindolyl together with a lower amount of 4-7′-, 7-7′-3-4′-, 3-7′-coupled dimers. To further understand the melanin structure, we investigated oxidative polymerization of DHICA under conditions of relevance to biomimetic processes. Four new linear trimers in eight atropoisomeric forms have been isolated and characterized giving the first evidence for the chiral nature of these early oligomeric species.