Glaucatotones A−I: Guaiane-type sesquiterpenoids from the roots of Lindera glauca with anti-inflammatory activity

• Published in: Bioorganic chemistry 2024-03, Vol.144, p.107135-107135, Article 107135
• Main Authors: Pan, Xinyuan, Cai, Jiayi, Liu, Kaohua, Guo, Jiaqi, Li, Siqi, Wang, Ling, Han, Lizhu, Zhou, Kexin, Meng, Xiongyu, Qin, Luping, Li, Huaqiang
• Format: Article
• Language: English
• Subjects: Anti-inflammatory; Cytotoxicity; Lindera glauca; Norsesquiterpenoids; Sesquiterpenoids
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107135

[Display omitted] •Nine new guaiane-type sesquiterpenoids were isolated from the roots of Lindera glauca.•Glaucatotone A (1) is a dihomosesquiterpenoid with an unprecedented 5/5/7/6 ring system.•(±)-Glaucatotone B (2a/2b) represent the first norsesquiterpenoids with a (cyclopentylmethyl)cyclohexane skeleton.•1, 2a, 2b and 7 exhibited potent inhibitory effects. Glaucatotones A − I, nine new guaiane-type sesquiterpenoids, along with two 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 (2a/2b), 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 guaiane-type norsesquiterpenoids. In vitro bioactivity, 2a selectively inhibited Bcap-37 with IC50 value of 5.60 μM, and 9 selectively inhibited Du-145 with IC50 value of 5.52 μM. The anti-inflammatory activity of 1–9 were tested, and of these compounds, 1, 2a, 2b and 7 exhibited potent inhibitory effects.