Study On The Secondary Metabolites And Their Biological Activities Of Four Symbiotic Fungi

Symbiotic fungi are microorganisms that live on the host for a long time and have a mutually beneficial symbiotic relationship with the host.To adapt to their unique living environment,the secondary metabolites produced from symbiotic fungi have novel structures and particular properties or functions,which have become a wide source of new drug molecules.Symbiotic fungi not only construct underground and above-ground symbiotic networks,but also connect these two symbiotic networks into a huge,complete,unified and coordinated global symbiotic network,to exert physiological and ecological efficiency more effectively and stabilize the global ecosystem.It plays an irreplaceable role in promoting the development of the human body,animals,plants,algae and other microorganisms,coevolution and increasing biodiversity of biological species.Therefore,it is of great significance to study symbiotic fungi.This dissertation consists of five chapters.The first four chapters discussed the secondary metabolites and biological activities of four symbiotic fungi Albifimbria viridis,Fusarium proliferatum,Fusarium oxysporum and Xylaria curta E10respectively.In chapter five,the fungal origin and biological activities of chromoone-chromoone dimer,chromoone-xanthone dimer and xanthone-xanthone dimer were reviewed.In this research,the secondary metabolites of four symbiotic fungi Albifimbria viridis,Fusarium proliferatum,Fusarium oxysporum and Xylaria curta E10 were studied.The separation methods involved included normal phase silica gel column chromatography,medium pressure column chromatography,gel column chromatography and high performance liquid chromatography.A total of seventy-three compounds were isolated from the solid（rice）fermentation broth of four symbiotic fungi,including twenty-one new compounds and fifty-two known compounds.The types of these compounds included macrolides,alkaloids,furandolenes,aglycolates,polyketones,steroids,simple aromatics and so on.The structures of the compounds were identified and analyzed by ¹H-NMR,¹³C-NMR,HSQC,HMBC,¹H-¹H COSY,ROESY,IR,UV,ORD,CD,MS,single-crystal X-ray diffraction and computational chemistry.Finally,the biological activities of the new compounds were studied.The endophytic fungi Albifimbria viridis and Fusarium proliferatum were isolated from the roots of Coptis chinensis Franch.Nineteen compounds were isolated from the solid（rice）fermentation broth of Albifimbria viridis,including three new alkaloids（1-3）and one new aromatic compound（4）.Fifteen compounds were known,including eight sesquiterpenes（5-12）,one steroid（13）,four alkaloids（14-17）and two aromatic compounds（18-19）.The activity experiment showed that compound 2 had inhibitory activity on LPS induced B lymphocyte proliferation.Compounds 8,10 and 12 had obvious cytotoxic activity on MCF-7 cells.Eighteen known compounds were isolated from the solid（rice）fermentation broth of Fusarium proliferatum.The compounds included three polyketones（20-22）,five alkaloids（23,26-27,30-31）,eight simple aromatic compounds（28-29,32-37）,one fatty acid ester compound（24）and one other compound（25）.Fusarium oxysporum is a symbiotic fungus with Bletilla striata.Thirteen compounds were isolated from the solid（rice）fermentation broth of Fusarium oxysporum,including three new polyketones（38-40）,one new furan polyene（41）and one new aglycolate ester（42）.Eight compounds were known,including one furan polyene（43）,three polyketones（44-47）,two aglycolates（48-49）and one lactone（50）.Compounds 38-41 showed weak inhibitory activity against Escherichia coli and Candida albicans.Xylaria is the largest genus in Xylariaceae,usually in the form of saprophytes and endophytes.Twenty-three compounds were isolated from the solid（rice）fermentation broth of Xylaria curta E10,including twelve new polyketones（51-62）.Eleven compounds were known,including three polyketones（63-65）,one diterpenoid（66）,one steroid（67）,two alkaloids（69-70）,three simple aromatic compounds（68,72-73）and one lactone（71）.The twelve new polyketones were all dimers with complex structures,involving two types of chroone-chroone dimer and chroone-oxanthrone dimer.Compound 51 showed inhibitory activity against Candida albicans,and compounds 58 and 60 showed inhibitory activity against Escherichia coli.In chapter five,chromoone-chromoone dimer,chromoone-xanthone dimer and xanthone-xanthone dimer were reviewed.The fungal origin and biological activities of these compounds were discussed to lay a foundation for finding drug lead compounds.