A new look at the rearrangement of adrenochrome under biomimetic conditions.

At physiological pH values, the rearrangement of adrenochrome leads, besides adrenolutin, to a major dimeric compound consisting of an adrenolutin moiety covalently linked to the angular 9-position of adrenochrome. When the reaction is carried out in air, the initially generated adrenolutin undergoes autoxidation to give 5,6-dihydroxy-1-methyl-isatin (DHMIs), which is smoothly oxidized to the 4,4'-dimer. Under an oxygen-depleted atmosphere, formation of these latter compounds is prevented, and the rearrangement of adrenochrome leads mainly to the adrenochrome dimer (about 50% yield) along with adrenolutin and 5,6-dihydroxy-1-methylindole (DHMI) in about 10% yield each. The product distribution is markedly dependent on the concentration of the aminochrome undergoing rearrangement, the nature of the buffer system used, and the pH of the medium. Heavy metal ions of common occurrence in biological systems, such as Cu2+, Zn2+, Co2+, significantly direct the reaction course towards the formation of adrenolutin, while Fe2+ and other cations with low redox potentials induce the almost exclusive formation of DHMI.