Studies On The Secondary Metabolites And Bioactivities Of Bipolaris Sp. And Aspergillus Terreus

This thesis consists of three parts.The first part mainly discusses the chemical composition of two strains Bipolaris zeicola and Bipolaris sp.TJ403-B1.In addition,the biosynthesis pathway of three novel types of sesterterpenoids derived from Bipolaris sp.TJ403-B1 and new skeletons of meroterpenoids isolated from Bipolaris zeicola were discussed.The isolated compounds were also screened for anti-HMGR,antibacterial,antiinflammatory,immunosuppressive,and cytotoxic activities.The second part was about the second metabolites of the coral endophytic fungus Aspergillus terreus and biological activities.The third part discusses the research progress of sesterterpenes in recent years,focusing on their source,skeleton types and biological activities.The genus Bipolaris,representing a large genus of filamentous fungi,encompasses hundreds of species and distributes worldwide.Bipolaris species are known to infect the graminicolous crops,such as wheat,rice,barley,and sorghum,to cause leaf spots,leaf lesions,root rots,and other disease symptoms,thus leading to colossal crop yield reduction.The phytotoxins produced by this plant pathogen have been investigated to better understand the chemical basis for plant disease susceptibility.Previous chemical investigations on the genus Bipolaris have demonstrated it to be particularly prolific sources of cochlioquinones,ophiobolins,terpestacins,and bipolenins,which contained plentiful structural backbones,including sesquiterpenes,sesterterpenes,and meroterpenes.Therefore,in order to further explore the metabolite diversities of Bipolaris sp.,we investigated the chemical components of Bipolaris zeicola and Bipolaris sp.TJ403-B1.We identified 49 compounds from the rice solid cultures of Bipolaris sp.TJ403-B1,of which 32 are new compounds.Most of them are ophiobolin type sesterterpoids.We discovered three types of sesterterpoid skeletons.One type was uniquely defined by a 5-6-6-5-fused carbocyclic skeleton decorated with an undescribed C-3–C-12 oxygen bridge to form a multicyclic caged system;one type featured an unprecedented 5-5-5-5-fused core skeleton;one type represented a new class sesterterpene-alkaloid hybrids.We evaluated the HMG-Co A reductase inhibition activity,anti-inflammatory,anti-microorganism,and cytotoxic activity.Some compounds have a significant inhibitory effect on hydroxymethylglutaryl-Co A reductase(HMGR),and some compounds have significant antibacterial activity.34 compounds were identified from the rice solid cultures of Bipolaris zeicola,including26 new compounds.These new compounds were characterized by a 1-alkylated-3,5-dihydroxyphenyl derivative coupled with a modified farnesyl pyrophosphate(FPP)unit.Structurally,five compounds possess a rare thiazole moiety;two compounds are the first examples of meroterpenoids featuring an undescribed 6/6/6/6/5 pentacyclic system,two compounds possess a rare thiazin moiety,and some of them showed significant inhibitory effects on the proliferation of T lymphocytes induced by concanavalin A.In addition,a total of 32 compounds were isolated and identified from the rice solid cultures of Aspergillus terreus,of which 17 ones were new,including four pairs of enantiomers and one racemate,and the structure of(±)-asperteretal D was corrected.Some compounds have a significant inhibitory effect on α-glucosidase.This research further enriched the secondary metabolites of Aspergillus terreus,and is also a supplement to the structures of γ-butenolides.