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

作者：Jun Yao, Chenyang Wang, Hanxiao Zeng, Yu Cao, Xianjie Qiu, Wenqi Li, Yongzhi Lu, Jinsai Shang, Jianping Wang, Yonghui Zhang, Zhengxi Hu · 发表于：Journal of Natural Products · 年份：2025 · DOI：10.1021/acs.jnatprod.5c00224 · 被引用次数：4 · 研究领域：Microbial Natural Products and Biosynthesis、Lichen and fungal ecology、Cancer Treatment and Pharmacology

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 EC 50 value of 4.1 ± 0.3 μM, suggesting its potential therapeutic application in the treatment of cholestasis.