Artemordosins A−L, cadinane-monoterpene heterodimers and sesquiterpenoids with antihepatoma activity from Artemisia ordosica

Abstract

Two unprecedented sesquiterpene and monoterpene heterodimers and ten previously undescribed sesquiterpenoids, artemordosins A−L (1−12), as well as ten known sesquiterpenoids (13−22), were obtained from Artemisia ordosica. Their structures were elucidated based on comprehensive analyses of NMR, IR, HRESIMS, GIAO NMR calculations with DP4+ probability analysis, and ECD calculations. Notably, artemordosins A and B (1 and 2) were the first examples of cadinane–monoterpene dimers, and artemordosin A (1) was a cadinane–myrceane heterodimer with a 6/6/6/6 ring system formed by [4 + 2] cycloaddition, while artemordosin B (2) was a 4,5-seco-cadinane-artemisane dimer connected through a C-5−O–C-4′ linkage. Artemordosin C (3) was the first example of 10(5 → 4)-abeo-eudesmane sesquiterpenoid featuring an unprecedented bicyclo[5.3.0]decane skeleton in natural products. Artemordosin B (2) and epi-deoxyarteannuin B (14) showed inhibitory activity on three hepatoma cells with IC₅₀ values of 37.1 and 15.4 μM (HepG2), 27.7 and 16.4 μM (Huh-7), 39.6 and 22.6 μM (SK-Hep-1).