Asperdoles A–N: Indole Diterpenoids from the Endolichenic Fungus Aspergillus sp. TJ403-YJ22

Fourteen new indole diterpenoids, designated as asperdoles A–N (1–14), were isolated from the endolichenic fungus Aspergillus sp. TJ403-YJ22. Notably, compounds 1–7 were characterized by the presence of 2-keto-3-hydroxy-oxidized indole moieties, which were connected to diterpenoid segments via methylene bridges. Compounds 1–5 featured fused 6/6/6 ring diterpenoid frameworks, whereas the tetrahydropyran in compounds 6–14 was cleaved, resulting in the formation of terminal vicinal diols in compounds 6–12 and olefinic double bonds in compounds 13 and 14. The planar structures and absolute configurations of these compounds were elucidated through a combination of NMR spectroscopy, HRESIMS, Snatzke’s method, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 4 exhibited selective FXR agonistic activity, with an EC50 value of 4.1 ± 0.3 μM, suggesting its potential therapeutic application in the treatment of cholestasis.