Isolation and stereospecific synthesis of indole alkaloids with lipid-lowering effects from the marine-derived fungus Colletotrichum gloeosporioides BB4

作者：Huang, Qin; Hao, Meng-Jiao; Wang, Lai-You; Wu, Feng; Li, Hou-Jin; Yuan, Jie; Xu, Jun; Mahmud, Taifo; Lan, Wen-Jian^*

来源：Phytochemistry, 2023, 209: 113612.

DOI：10.1016/j.phytochem.2023.113612

• Colletotrichum gloeosporioides
• Marine -derived fungus
• Stereospecific synthesis
• Lipid -lowering effects

Seven undescribed compounds, colletotrichindoles A-E, colletotrichaniline A, and colletotrichdiol A, as well as three known compounds, (-)-isoalternatine A, (+)-alternatine A and 3-hydroxybutan-2-yl 2-phenylacetate were isolated from the marine-derived fungus Colletotrichu gloeosporioides BB4. The racemic mixtures colleto-trichindole A,colletotrichindole C, and colletotrichdiol A were further separated by chiral chromatography to give three pairs of enantiomers (10S,11R,13S)/(10R,11S,13R)-colletotrichindole A, (10R,11R,13S)/ (10S,11S,13R)-colletotrichindole C, and (9S,10S)/(9R,10R)-colletotrichdiol A, respectively. The chemical structures of seven undescribed compounds and the known compounds, (-)-isoalternatine A, and (+)-alternatine A were determined using a combination of NMR, MS, X-ray diffraction, ECD calculations, and/or chemical synthesis. All possible enantiomers of colletotrichindoles A-E were synthesized and used to determine the ab-solute configurations of the natural products by comparing their spectroscopic data and HPLC retention times on a chiral column. In addition, the X-ray crystal structures of the known compounds (-)-isoalternatine A and (+)-alternatine A were also obtained to confirm their absolute configurations. (10S,11R,13S)-Colletotrichindole A, colletotrichindole B, and (+)-alternatine A significantly reduced triglyceride levels in 3T3-L1 cells with EC50 values of 5.8, 9.0, and 1.3 & mu;M, respectively.

• 单位
  广东省人民医院; 广东药学院; 中山大学