Selective Enzymatic C−H‐Oxyfunctionalization for the Efficient Synthesis of Grevillic Acid

Abstract In this study, a selective C−H‐oxyfunctionalization using an unspecific peroxygenase (UPO) enabled an efficient biosynthetic route for the synthesis of grevillic acid (GA), a natural antioxidant. The route commenced with the release of o ‐coumaric acid (oCA) from trans ‐2‐coumaric acid glucoside ( trans ‐CAG) using commercially available β‐ glucosidase from almonds. In addition, a cis ‐to‐ trans photoisomerization of cis ‐CAG was implemented to increase the synthetic access of oCA. The key step, the para ‐hydroxylation relative to the existing hydroxyl group of oCA, was accomplished by an UPO with full conversion and 93% isolated yield. Despite its name, the UPO turned out to exhibit excellent regioselectivity in this C−H functionalization, requiring only H 2 O 2 as a cosubstrate.