Rare 7,9-dinorlignans with neuroprotective activity from the roots of Lindera aggregata (Sims) Kosterm

Linderagatins C-F (1-4), the first examples of naturally occurring diaryltetrahydrofuran-type 7,9 '-dinorlignans, were characterized from the roots of Lindera aggregata (Sims) Kosterm. The structures of these dinorlignans were elucidated by extensive spectroscopic analysis. The absolute configurations were determined based on calculated and experimental ECD data. A biosynthetic pathway for these dinorlignans was hypothetically proposed. Compounds 2 and 3 showed significant neuroprotective effects on erastin-induced ferroptosis in HT-22 cells with EC50 values of 23.4 and 21.8 mu M, respectively.