Studies On The Chemical Constituents And Bioactivities Of Aspergillus Ochraceus And Aspergillus Ustus

Three chapters were included in the dissertation.In the first chapter,the secondary metabolites of Aspergillus ochraceus were systematic studied.The anti-inflammatory activities screening of some identified secondary metabolites obtained from A.ochraceus were performed.In the second chapter,the secondary metabolites of Aspergillus ustus were systematic studied.PTP1 B inhibitory activities of selected compounds from A.ustus were evaluated.In the third chapter,structural diversity and biological activities of indole diketopiperazine alkaloids from fungi were summarized from 1944 to 2017.Indole diketopiperazine alkaloids including indole ring and diketopiperazine moieties are the major metabolic products of fungi.Indole diketopiperazine biogenetically derived from tryptophan.Indole diketopiperazine alkaloids exhibit diverse structures and numerous biological activities.Because N-1,C-2,C-3,C-5,C-6,C-7 were often substitued by some units,frequently by one or more prenylated units.In addition,some core were formed through an intramolecular hetero Diels-Alder reaction.Indole diketopiperazine alkaloids have been an area of intense research for decades due to the vast structural diversity and biological activities of these secondary metabolites.A.ochraceus is notorious for the metabolite ochratoxin A(OTA),which lead to teratogenicity,mutagenesis,and carcinogen.In recent years,the phytochemical investigation of A.ochraceus led to the isolation of a large number of indole alkaloids,polykethers,pyrazinones,circumdatins,sesquiterpenoids,and steroids,apart from OTA.Indole alkaloids,especially indole diketopiperazine alkaloids containing a unique bicyclo[2.2.2]-diazaoctane ring system,have become the focus of our research.A.ochraceus was phytochemically investigated,which led to the isolation and characterization of 12 compounds,including 3 new ones and 1 new natural product.The in vitro anti-inflammatory effects of some identitied compounds were investigated by using LPS-stimulated murine macrophage RAW 264.7 cells.In addition,the secondary metabolites of A.ustus were systematic studied.Through extensive literature research,the results showed that the main secondary metabolites of A.ustus were meroterpenoids,sesquiterpenes,ophiobolins,alkaloids,steroids and other compounds.During 1970 s and 1980 s,the biosynthesis of meroterpenoids were discussed.With the development of separation technology and the discovery of biosynthetic gene clusters,it is necessary to study the secondary metabolites of A.ustus again.By means of comprehensive application of various chromatographic separation techniques,spectral analytical techniques,single crystal diffraction and quantum chemical calculations,A.ustus was phytochemically investigated and led to the isolation and characterization of 54 compounds,including 21 new ones and 5 new natural products.PTP1 B inhibitory activities of some compounds were evaluated.Some resorcinol and its resorcinoloside phenolic acid compounds were first isolated from A.ustus.The discovery of these compounds greatly enriched the secondary metabolites of A.ustus.Structurally,the natural products contained one or more hydroxyl group and diverse changes in side chain.In addition to their structural diversity and a variety of bioactivities were also present for these analogues compounds,including but not limited to antioxidant,metalloproteinase-inhibiting,PTP1 B inhibitory activities,and human leukocyte elastase inhibitor.Therefore,this kind of phenolic acid compounds need further study.