Glaucatotones A−I: Guaiacane-Type Sesquiterpenoids from the Roots of Lindera Glauca with Anti-Inflammatory Activity

Glaucatotones A−I, nine new guaiacane-type sesquiterpenoids, along with the reported compounds, namely (1β,5β)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (10) and pseudoguaianelactone C (11), were isolated from the roots of Lindera glauca. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of experimental and calculated electronic circular dichroism (ECD) data. Structurally, glaucatotone A (1) is characterized as a dihomosesquiterpenoid with an unprecedented 5/5/7/6 ring system. A pair of enantiomers, (±)-glaucatotone B (2), represent the first rearranged norsesquiterpenoid with a (cyclopentylmethyl)cyclohexane skeleton. 3 is defined as a dinorsesquiterpenoid possessing a 5/7/5 ring system. 4−6 are three guaiacane-type norsesquiterpenoids, 4 and 5 are a pair of stereoisomers. In vitro bioactivity, (−)-2 and 9 selectively inhibited Bcap-37 and Du-145 cells with IC50 values of 5.6 and 5.5 μM, respectively. The anti-inflammatory activity of 1−9 were tested, and of these compounds, 1, (±)-2 and 7 exhibited potent inhibitory effects.