Structures And Activities Of Secondary Metabolites From Four Deep-Sea-Derived Fungi

The deep-sea environments account for 95%of the ocean which covers 71%of the Earth’s surface area.Marine fungi are important components of marine microorganisms.In order to adapt to the extreme environment of the deep sea,marine fungi living here have a unique metabolic mechanism,and are more capable of producing secondary metabolites with novel chemical structures and unique biological activities.Therefore,the study of deep-sea marine fungi can enrich our knowledge of secondary metabolites from deep-sea microorganisms and provides scientific basis for the exploration and development of marine biological resources.In this study,86 strains of marine fungi were isolated from deep-sea sediments samples.Based on the screening of chemical component and biological activities,Cladosporium cladosporioides 8-1,Talaromyce sp.Z2,Trichoderma lixii R22 and T.saturnisporum R6 were selected as the subjects for the study of secondary metabolites.Their secondary metabolites were purified by repeated column chromatography on silica gel,RP-18 and Sephadex LH-20 and preparative thin-layer chromatography as well as semi-preparative HPLC.The structures of the compounds were identified by spectroscopic techniques,such as 1D/2D NMR,ECD,IR,MS and UV,as well as by comparision with literatures.Efforts on C.cladosporioides 8-1 results in the isolation and identification of 25compounds,including eight new compounds（CC1-CC4 and CC7-CC10）and three new naturally-occuring products（CC5,CC6 and CC11）.Especially CC1 with a novel sulfur-containing carbon skeleton,and CC2 is a new iodinated dimeric naphtho-γ-pyrone.17 compounds were separated and elucidated from Talaromyce sp.Z2,including a new sorbicillin derivative（TP1）,which was found from Talaromyce sp firstly.T.lixii R22 gave 29 compounds,including five new lipid derivatives（TL1-TL5）.14 compounds were characterized from T.saturnisporum R6,with structural types covering terpenoids,steroids and polyketides.Some of the compounds were evaluated for biological activities.The results showed that sorbicillin derivative TP1 exhibited growth inhibition of the Gaeumannomyces graminis with MIC value of 25μg/m L,and lipid derivatives TL1and TL2 showed inhibitory effects against Fusarium graminearum with MIC value of25μg/m L.Compounds CC6-CC8 showed moderate inhibitory activity against one of the experimental marine pathogens,with inhibition zone diameters exceeding 10 mm.The polyketide derivative CC1 showed significant inhibitory activity against Prorocentrum donghaiense with IC₅₀ values of 3.8μg/m L.Compounds CC2,CC4 and TL4 could remarkably inhibit the growth of Heterosigma akashiwo,and the IC₅₀ values ranged from 3.5 to 5.6μg/m L.These secondary metabolites with potent biological activities can provide a scientific basis for the preparation of bioactive agents.In this dissertation,studies on the chemical structures and biological activities of the secondary metabolites from four deep-sea fungi.Totally,85 compounds including14 new ones and 3 naturally-occuring products were purified and identified,with structural types covering polyketides,terpenoids,steroids,alkaloids,diketopiperazines.The diversity of secondary metabolites could effectively enrich the study of deep-sea natural products and further provide theoretical references for understanding the metabolic mechanisms of deep-sea-derived fungi.The screening of compounds with potent biological activities can provide scientific basis for the development and utilization of deep-sea marine biological resources.