Synthesis of optically active tetrameric melanin intermediates by oxidation of the melanogenic precursor 5,6-dihydroxyindole-2-carboxylic acid under biomimetic conditions

Abstract In a recent work addressing the structural characterization of melanin pigments, we reported the isolation and characterization of trimeric oligomers of 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a key intermediate in the biosynthesis of the dark brown eumelanins, by tyrosine catalyzed oxidation of the indole under biomimetic conditions. These oligomers feature atropisomerism and consequently, we wished to investigate chirality in such systems. Herein, we report two significant steps forward in this study: The isolation of a regiosymmetric DHICA tetramer by means of a model approach involving oxidation of the main DHICA dimer, namely 4,4′-biindolyl and the first resolution of eumelanin intermediates. This also allowed the absolute stereochemistry of the newly isolated tetramer to be defined by applying the exiton chirality method.