Cyathstrines A–K, Structurally Diverse Polycyclic Polyoxygenated Cyathane Diterpenoid Xylosides with Antibacterial and Neuroprotective Activities from the Fungus Cyathus striatus

A chemical investigation of the basidiomycete Cyathus striatus led to the isolation of 17 polyoxygenated cyathane diterpenoid xylosides, cyathstrines A–K (1–17), including 11 new ones sharing five distinct ring skeletons, two sesquiterpenoids (18 and 19), and two lupane triterpenoids (20 and 21), as well as three sterols (22–24), based on the OSMAC (One Strain–Many Compounds) strategy. Among them, compound 5 represents the first example of cyathane diterpenoids with an undescribed 5/6/7/6/5/6/6-fused ring skeleton incorporating an extra 2H-pyran moiety, and compound 7 bears an unconventional 9/7/6/5/6-fused pentacyclic ring skeleton. The structures of these compounds were elucidated by means of NMR spectroscopic analyses, HRESIMS and ECD calculations. Compounds 7 and 9 exhibited moderate antibacterial effects against six human pathogenic bacteria, with MIC values ranging from 8 to 32 μg/mL. Meanwhile, compound 8 showed significant neuroprotective activity at 20 μM, with cell viability improved to 82.4% from the MPP+-treated cell viability of 51.20%, which was comparable to the positive control. Additionally, compounds 3, 13, 15, and 17 demonstrated notable neuroprotective effects, with cell viabilities of more than 70%. These findings expanded the chemical space of cyathane diterpenoids and provided the new template molecules for the development of anti-infective and neuroprotective drugs.