Oxidative coupling of coumarins by blue-led-driven in situ activation of horseradish peroxidase in a two-liquid-phase system

A blue-LED-driven two-liquid-phase system has been set up for the in situ activation of horseradish peroxidase avoiding the use of hydrogen peroxide and drawbacks related to enzyme denaturation and undesired radical side-reactions. The photobiocatalytic system was applied for the oxidative coupling of natural and synthetic coumarins to bicoumarins, allowing to obtain homodimers in only one step, avoiding the use of tedious protecting groups. Two natural C-2 symmetric bicoumarins derived from the coupling of scopoletin were synthesized for the first time. UV-visible spectrophotometry analysis confirmed the radical-free and blue-LED-driven in situ oxidation of the green solvent 2-methyltetrahydrofuran to the corresponding hydroperoxide, which in turn oxidizes the ferric heme of horseradish peroxidase to ferryl intermediate, triggering the oxidative coupling reaction.