The Secondary Metabolites Of Two Entophytic Penicillium And Microbial Fermentation Of Two Traditional Chinese Medicines

The structures of secondary metabolites produced by endophyte fungus which is one of significant source of natural products,were complicated and varied.This paper focus on the secondary metabolites of two endophyte fungi(Penicillium roqueforti and Penicillium expansum)separated from Aconitum vilmorinianum Kom and their bioactivities were also investigated.The isotope-incorporation studies were performed to investigate the proposed chemical mechanism for the generation of some new terpenoids.Then,we aimed at the microorganism fermentation of Gardenia jasminoides and Asparagus filicinus by Penicillium roqueforti.In the end of this thesis,the studies of biosynthesis of terpenoids were summarized.The first chapter of this thesis focus on the secondary metabolites of P.roqueforti.14 compounds included 8 new sesterterpenoids,peniroquesines D-K were isolated.Peniroquesine K was a sesterterpenoid possessed unprecedented 5-6-5-6-5-fused pentacyclic ring system.The absolute configurations of these new compounds were established based on Mosher's method and X-ray analysis.Peniroquesines A-D,H and J-K showed potent cytotoxic activities.Peniroquesines A-B,H and J-K also showed a potent inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages.The chemical mechanism of some new terpenoids was investigated by isotope-labeling experiments.The results showed that various Wagner-Meerwein rearrangement(WMR),a triple WMR,a type-? dyotropic rearrangement(DTR)and a 1,3-H shift were occurred during the cyclization of the new sesterterpenoids from GFPP.In the second chapter,exPanstines A-E were 5 novel isoprenoid epoxycyclohexenones featuring two different polycyclic skeletons from Penicillium expansum.Especially for expanstines D-E,they both possessed an unusual oxetane ring.The absolute configurations of these new compounds were established based on X-ray analysis and ECD experiments.In additional,expanstines D and E exhibit selective antibacterial activity against B.subtilis with MIC of 0.25 ?g/mL.Further investigation of photosensitivity of 4'-oxomacrophorin A 7'-acetate(6)and 4'-oxomacrophorin A(7)showed that 1-3 and 4-5 were transformed from 6-7,which plausibly underwent a[2+2]Paterno-Buchi photo-addition and an unusual intramolecular photo-ene reaction respectively.In chapter 3 and 4,the microorganism fermentation of Gardenia jasminoides and Asparagus filicinus by P.roqueforti were investigated.The results revealed that the main component of G.jasminoides,geniposide,can be converted into three new diastereomers(genitines A-C)and a known compound(genipin)by P.roqueforti.The results of bioactivities assays showed that both genipin and the mixture of genitines A-C exhibited stronger cytotoxic and anti-inflammatory activities than geniposide.From root of A filicinus,a new steroid,aspafilisine,with unique rearranged seven-membered B ring and 22 known compounds were isolated.The fermentation of A.filicinus by P.roqueforti also was administered.In additional,NMR was used for characterization of chemical changes of non-fermented and fermented A.filicinus with P.roqueforti.In the end of this thesis,the study of biosynthesis of sesquiterpenes,diterpene and sesterterpenes which published in authoritative journal from 2010 to 2018 were reviewed and summarized.