Secondary Metabolites From Three Marine-derived Trichoderma Fungi And Their Bioactivities

Due to the unique structures and potent bioactivities, natural products of marine-derived Trichoderma origin continued to be the rich resources of new leading compounds and functional agents. In this dissertation, three marine-derived Trichoderma fungi(Trichoderma asperellum dl34 、 T. citrinoviride cf27 and T. harzianum R5) were screened under different media. The fermentation extracts were evaluated on the basis of thin layer chromatography(TLC), high performance liquid chromatography(HPLC) and bioassay. As a result, suitable media were selected for further investigation of chemical constituents. Most of the isolates were preliminarily screened for their bioactivities.The compounds were isolated by repeated column chromatography on silica gel, reversed-phase silica gel, and Sephadex LH-20, preparative TLC, and semi-preparative HPLC as well as recrystallization. Their structures were elucidated by means of spectroscopic methods including 1D/2D-NMR, MS, IR, ECD and by quantum chemical calculation methods. A total of 55 compounds including 4 new ones were isolated and identified.From the cultures of T. asperellum dl34, 18 compounds were isolated and identified, including one new diterpenoid(TA1), one known diterpenoid(TA2), ten known steroids(TA3~TA12), two diketopiperazines(TA14 and TA15), one nucleotide(TA16) and three polyketides(TA13, TA17 and TA18). 23 compounds were isolated and identified from the cultures of T. citrinoviride cf27, including one new diterpenoid(TC1), one new norditerpenoid(TC2), five known triterpenoids(TC3~TC7), one sesquiterpene(TC8), four steroids(TC9~TC12), eight polyketides(TC13~TC20), and two alkaloids(TC21 and TC22). 14 compounds including one new terpenoid(TH1), six known sterols(TH2~TH7), two known polyketides(TH8 and TH9), two alkaloids(TH10 and TH11), and two nucleotides(TH13 and TH14) were isolated and identified from the cultures of T. harzianum R5.Most of the isolated compounds were screened for biological activities, including inhibition against bacteria, phytopathogenic fungi, marine zooplankton, and marine phytoplankton, and some of them showed significant activities. The results showed that TC2 inhibited the growth of Staphyloccocus aureus with an MIC value of 12.4 μg/m L; TA1、TA2、TC2 and TH1 were toxic to Artemia salina with LC50 value of 12.0、38.2、65.6 and 68.6 μg/m L; TC2 exhibited 37.2、23.4 and 14.1% inhibition of Chattonella marina, Heterosigma akashiwo, and Prorocentrum donghaiense at 100 μg/m L, respectively; TC1 and TC13 exhibited 54.1 and 36.7% inhibition of P. donghaiense at 100 μg/m L, respectively.In this dissertation, secondary metabolites of three marine-derived Trichoderma fungi were thoroughly studied. It enriched the chemical diversity of marine natural products and may provide important proof to the utilization and exploration of marine Trichoderma-derived natural products.