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

Abstract: In this study, a selective C􏰀 H-oxyfunc- tionalization 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 H2O2 as a cosubstrate. Keywords: Antioxidants; Biocatalysis; Hydroxyla- tion; Photoisomerization; Unspecific peroxygenase