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.