Study On The Active Secondary Metabolites Of Aspergillus Terreus And A Strain Of Endophytic Streptomyces Gastrodiae

There are thousands of novel secondary metabolites in recent reports that resarchers have discoveried and purified numerous compounds which are bioactive and unique structure in Aspergillus genus.Hence,somes scientists coming from different countries have paid much attention to the secondary metabolites isolated from this genus.We summarized rencently bioactive metabolites derived from Aspergillus genus in chapter one of this thesis.In chapter two of this dissertation,we mainly focused on chemical screening towards 100 strains of fungus derived from Tibetan soil and 40 strains of actinomycetes which are isolated from Gastrodia elata Bl.and Tibetan soil respectively.Combining TLC chemical screening with re-screening of target strains fermented in different culture borth,we selected two strains(Asperigillus terreus 13-3N isolated from Tibetan soil and Streptomyces coelescens YT-2 isolated from Gastrodia elata Bl.)as researching and cultivation target.In chapter three of this dissertation,we isolated crude extracts obtained from the large-scale cultivation of Asperigillus terreus 13-3N by different means of purification,meanwhile we determined structure of some compounds purified from crude extracts by a combination of NMR spectroscopy and mass spectrometry.Finally we have studied on the secondary metabolites of Aspergillus terreus13-3N isolated from Tibet plateau and obtained fifteen compounds,compound 1(decanoic acid,(2,2-dimethyl-1,3-dioxolan-4-yl)methyl ester)was first isolated from natural products.Compounds 9(R(-)-glycerol monolinoleate),13(lactariamide B),14(cyclo-(L-Leu-L-Trp))and 15(cyclo-(trans-4-hydroxyl-L-Pro-L-Phe))were isolated from the Asperigillus for the first time.Other known compounds:4,5-dimethylresorcinol(2),indole-3-acetic acid(3),aspulvinone H(4),dihydroisoflavipucine(5),14-hydroxyterezine D(6),terezine D(7),cyclo-[L-(4-hydroxylprolinyl)-L-leucine](8),5a,8a-epidioxyergosta-6,22-dien-3?-ol(10)were also isolated.The antimicrobial activities of compounds 4-9,12-13 were tested by the broth microdilution method in 96-well culture plates.Compound 4 showed significant antimicrobial activities against S.aureus and B.subtilis with MIC values at 8?g/mL and 64 ?g/mL respectively.Compound 9 showed obvious antimicrobial activities against S.aureus and B.subtilis with MIC values at 32 ?g/mL and 32 ?g/mL,respectively.Nystatin and Kanamycin were used as positive control to the pathogenic fungi and bacterial with MIC values at 32 ?g/mL and 32 ?g/mL,respectively.In chapter four of this eassy we isolated crude extracts obtained from the large-scale cultivation of Streptomyces coelescens YT-2 by different means of purification,meanwhile we determined structure of some compounds purified from crude extracts by a combination of NMR spectroscopy and mass spectrometry.Finally we studied on the secondary metabolites of Streptomyces coelescens YT-2 isolated from Gastrodia elata and obtained six known compounds:cyclo-(L-Pro-L-Ile)(1),cyclo(L-Pro-L-Phe(2),germicidin(3),3-(4-hydroxyphenyl)propanoic acid methyl ester(4),benzeneacetic acid(5)and 4-hydroxybenzaldehyde(6).