Biomimetic synthesis and anti-inflammatory effects of horsfiequinone A.

• A biomimetic total synthesis of horsfiequinone A. • Aerobic copper-catalyzed oxidation. • The anti-inflammatory activity of horsfiequinone A was revisited. Inspired by the oxy-tyrosinase type II copper enzyme, a biomimetic synthesis of the natural product horsfiequinone A (1) has been achieved using CuOTf/DBED/O 2 catalyzed oxidation as a key step. The synthetic route furnished 1 in 33% overall yield (64% brsm) from commercially available para-hydroxybenzaldehyde. Moreover, revisiting the biological activity of 1 resulted in the discovery of its in vitro inhibitory activity towards nitric oxide (NO) production in LPS-induced RAW264.7 cells with an IC 50 value of 4.42 ± 0.81 μM. The anti-inflammatory effect of 1 was further supported by an iNOS expression inhibition assay and molecular docking simulation. [ABSTRACT FROM AUTHOR]