Chemoenzymatic Cyclization by Vanadium Chloroperoxidase for Synthesis of 4-Hydroxyisochroman-1-ones.

Abstract

4-Hydroxyisochroman-1-ones belong to the class of the secondary metabolite 3,4-dihydroisocoumarins. They exhibit a wide range of biological activities. These compounds can be synthesized through halocyclization using hypervalent iodine species or N-bromosuccinimide, followed by hydrolysis. Nonetheless, the reactions required specific conditions and generated toxic byproducts. In this study, Curvularia inaequalis vanadium chloroperoxidase (CiVCPO) catalyzed the chemoenzymatic cyclization of 2-vinylbenzoic acids with different electron-donating groups (1a-1e) to produce good yields of 4-hydroxyisochroman-1-ones (3a-3e) by adding KBr and H2O2 in citrate buffer (pH 5). The reaction mixture contained 30% DMSO to improve substrate solubility without enzyme activity loss. The condition is more environmentally friendly than chemical methods. Therefore, it offers an alternative approach for synthesizing 4-hydroxyisochroman-1-ones.