Synthesis of gentianine N-oxide by enzymatic hydrolysis of swertiamarin in the presence of hydroxylamine and reaction pathway to gentianine and gentianol

摘要

Gentianine is a metabolite of gentiopicroside and swertiamarin. Several biological activities have been reported for gentianine, such as antiinflammatory and antidiabetic activity, and hypotensive effect. Gentiopicroside is found in 0.9-9.8% content in Gentian root or Gentian scabra root, and Swertiamarin is contained in Swertia herb in 2-10%. These natural products can be potential starting materials for the synthesis of gentianine. This study describes the beta-glucosidase-catalyzed hydrolysis of gentiopicroside and swertiamarin in the presence of hydroxylamine to afford gentianine N-oxide, which can be a synthetic precursor of gentianine derivatives. Enzymatic hydrolysis of swertiamarin selectively afforded gentianine N-oxide in 81% yield, whereas gentiopicroside afforded gentianine N-oxide and gentianol N-oxide. Plausible reaction pathways leading to gentianine, gentianol, and their N-oxides were also investigated. (C) 2019 Elsevier Ltd. All rights reserved.