Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266071, People's Republic of China.
The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, People's Republic of China.
J Org Chem. 2023 Mar 3;88(5):3185-3192. doi: 10.1021/acs.joc.2c02983. Epub 2023 Feb 22.
Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus F5 guided the isolation of five novel cytochalasans, chamisides B-F (), and two known ones, chaetoconvosins C and D ( and ). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system. Remarkably, compound with a relatively flexible side chain showed promising inhibition activity against the cholesterol transporter protein Niemann-Pick C1-like 1 (NPC1L1), expanding the function of cytochalasans.
基于质谱（MS）的内生真菌 F5 的代谢物分析指导了五种新型细胞松弛素的分离，分别为 chamisides B-F（），以及两种已知的 chaetoconvosin C 和 D（和）。通过 MS、核磁共振和单晶 X 射线衍射分析，明确了它们的结构，包括立体化学。化合物共享细胞松弛素中新型的 5/6/5/5/7 稠合五环骨架，被合理地提出为与共分离的具有 6/6/5/7/5、6/6/5/5/7 或 6/6/5 环系统的细胞松弛素有关的关键生物合成前体。值得注意的是，具有相对灵活侧链的化合物对胆固醇转运蛋白 Niemann-Pick C1 样 1（NPC1L1）显示出有希望的抑制活性，扩展了细胞松弛素的功能。
