Modified Eremophilanes from Parasenecio hastatus and Their Neuroprotective Activities

The new modified eremophilanes hastatusins A–K (1–11) and 13 known compounds (12–24) were isolated from Parasenecio hastatus. The structures of 1–24 were elucidated based on spectroscopic data analysis and comparison with literature data. The absolute configurations of compounds 1 and 2 were defined by single-crystal X-ray diffraction analysis, and the other new compounds were assigned based on ECD data. This work is the first report of the crystal structure of an 8,9-seco-eremophilanolide (1) with two lactone units. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (−)-1 and (+)-1 were established via experimental and calculated ECD data. The new compounds represent four unusual skeletons: a modified 8,9-seco-eremophilane featuring a rare 6,9;8,12-dilactone moiety (1), a furanoeremophilane-type skeleton (2–7, 11), a rare C14 nor-eremophilane-type skeleton (8, 9), and a modified eremophilane lactone-type skeleton (10). All isolates were assayed for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury, and compounds 2–5, 12, 21, and 23 exhibited activities even at a low concentration of 1 μM. Compounds 6–9, 13, 14, 17, 20, 22, and 24 also showed notable effects at 10 and 100 μM.本研究从戟叶蟹甲草（Parasenecio hastatus）中分离得到11个新的修饰型艾里莫芬烷（eremophilanes）类衍生物hastatusins A~K（1~11），以及13个已知化合物（12~24）。通过光谱数据分析并与文献数据比对，阐明了1~24所有化合物的化学结构。化合物1与2的绝对构型通过单晶X射线衍射（single-crystal X-ray diffraction）分析确定，其余新化合物的绝对构型则通过电子圆二色谱（Electronic Circular Dichroism, ECD）数据推定。本工作首次报道了带有两个内酯单元的8,9-开环艾里莫芬烷内酯（8,9-seco-eremophilanolide）类化合物（1）的晶体结构。通过手性相高效液相色谱（chiral-phase High Performance Liquid Chromatography, HPLC）分离得到了化合物1的对映异构体，并结合实验与计算得到的ECD数据确定了(-)-1与(+)-1的绝对构型。新化合物共涵盖4种罕见骨架：一是带有稀有6,9;8,12-双内酯基团的修饰型8,9-开环艾里莫芬烷骨架（1），二是呋喃艾里莫芬烷型骨架（2~7、11），三是罕见的C14去甲艾里莫芬烷型骨架（8、9），四是修饰型艾里莫芬烷内酯型骨架（10）。对所有分离得到的化合物进行了抗过氧化氢（H₂O₂）诱导的SH-SY5Y细胞损伤的神经保护活性筛选，结果显示化合物2~5、12、21及23在1 μM的低浓度下即表现出显著活性。化合物6~9、13、14、17、20、22及24在10 μM与100 μM浓度下同样展现出明确的神经保护效果。