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.