Neuroprotective Guanacastane Diterpenoids from the Endophytic Fungus Candolleomyces sp.

Twenty novel guanacastane diterpenoids candollins A-T (1-20) were isolated from Candolleomyces sp. cultured on agar solid medium. The structures were elucidated according to the NMR, HRESIMS, and electronic circular dichroism spectra. Compounds 1 and 3 were further confirmed by X-ray crystallography. Compound 1 was an unprecedented C19 norditerpenoid containing a 3-methyl-2(3H)-furanone constitutional unit. Compounds 2-6, 8, and 9 were C19 norditerpenoids with respective demethylation at C-18, C-4, and C-8. Compound 7 was a novel C17 norditerpenoid with deisopropyl at C-12. Compounds 10, 11, and 16 had a novel methyl propionate substituent at C-4, a novel 6/7/5/5-fused tetracyclic ring, and an unprecedented 5/6/7/6-fused tetracyclic backbone, respectively. Compounds 4-10, 14, 15, and 17-19 showed significant neuroprotective effects with a survival rate of 68.32-97.53% at 20 μM. The neuroprotective activities of compounds 7 and 10 were positively correlated with the concentration. Compounds 6 and 8 showed neuroprotective effects with survival rates of 76% and 74% at a minimum concentration (0.25 μM), respectively.