Peroxidase-catalyzed coupling of solid-supported ortho-methoxyphenols

Enzyme-catalyzed C-C bond formation has been performed on solid-supported phenols, thereby expanding the repertoire of enzymatic catalysis on resin-bound substrates. In the presence of hydroquinone bound to various commercial resins, soybean peroxidase catalyzed the coupling of apocynin (acetovanillone) to give dimers, trimers, and oligomers with structures similar to what is obtained in solution-phase reactions. In addition to phenolic coupling, peroxidase catalyzed a Fries rearrangement presumably due to rearrangement of the acyl phenolic radicals generated on the solid phase through peroxidase catalysis. This represents the first enzymatic Fries rearrangement reported to date. Together with the solid-phase biocatalytic phenolic coupling, these results provide a route to the further expansion of enzymatic catalysis in combinatorial library synthesis.