Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, PR China.
Phytochemistry. 2020 Mar;171:112234. doi: 10.1016/j.phytochem.2019.112234. Epub 2020 Jan 2.
A total of fifteen grayanane diterpenoid glucosides including eight undescribed ones, pierisjaponosides A-H, were isolated from the leaves of Pieris japonica (Thunb.) D. Don ex G. Don (Ericaceae). Their structures were established by extensive spectros copic techniques including HRESIMS and NMR, as well as chemical methods. The absolute configurations of pierisjaponosides A, B, and D were finally established by single-crystal X-ray diffraction with Cu Kα radiation. This is the first time to report the crystal structure of a 5,9-epoxygrayanane diterpenoid glucoside. Pierisjaponoside E represents the first example of a 9β-hydroxygrayan-1(10)-ene diterpenoid. All the isolated grayanane diterpenoid glucosides were evaluated for their analgesic activities in the acetic acid-induced writhing models in mice, and showed significant analgesic effects. Pierisjaponosides A and C-H, micranthanoside A, pieroside A, and craiobiosides A and B displayed significant analgesic effects with the writhe inhibition rates over 50% at a dose of 5.0 mg/kg. Pierisjaponoside E exhibited significant analgesic activities with the percentage inhibitions of 81.7%, 70.4%, and 52.1% at the doses of 5.0, 1.0, and 0.2 mg/kg, respectively. The preliminary structure-activity relationships of grayanane diterpenoid glucosides as potent analgesics were discussed, giving some clues to design novel analgesics.
总共从报春花属植物（Ericaceae）的叶子中分离出了十五种新的钩藤二萜糖苷，包括八种未描述的钩藤二萜糖苷，即报春花苷 A-H。通过广泛的光谱技术，包括高分辨率电喷雾电离质谱（HRESIMS）和 NMR 以及化学方法确定了它们的结构。通过单晶 X 射线衍射法，使用 Cu Kα 辐射，最终确定了报春花苷 A、B 和 D 的绝对构型。这是首次报道 5,9-环氧钩藤二萜糖苷的晶体结构。报春花苷 E 代表了第一个 9β-羟基钩藤-1(10)-烯二萜。所有分离出的钩藤二萜糖苷均在醋酸诱导的小鼠扭体模型中评估了其镇痛活性，表现出显著的镇痛作用。报春花苷 A 和 C-H、米团苷 A、报春苷 A 以及刺五加苷 A 和 B 在 5.0 mg/kg 剂量下扭体抑制率超过 50%，表现出显著的镇痛作用。报春花苷 E 在 5.0、1.0 和 0.2 mg/kg 剂量下的抑制率分别为 81.7%、70.4%和 52.1%，表现出显著的镇痛活性。讨论了钩藤二萜糖苷作为有效镇痛剂的初步结构-活性关系，为设计新型镇痛药提供了一些线索。
