Studies On Secondary Metabolites And Bioactivities Of Penicillium Canescens And Trichoderma Citrinoviride

The paper is divided into three chapters.The first chapter mainly discusses the chemical constituents and biological activities of Penicillium canescens.The second chapter describes the secondary metabolites and biological activities of Trichoderma citrinoviride.The third chapter reviews the research progresses of polyketides derived from Penicillium fungi in recent literature.At present,there are few studies on Penicillium canescens,only about 20 secondary metabolites have been reported,and some xanthones show strong hypoglycemic activity.Therefore,we have carried out in-depth research on secondary metabolites of P.canescens.As a result,17 compounds were isolated and identified from solid cultures,among which 10were new compounds.Compounds 1–5 are new skeleton compounds of aromatic polyketone dimers bearing unprecedented 5/6/6/6/5 heterocyclic chemical architectures with a rare pentacyclic dihydrobenzo[1,4]dioxine core,including three pairs of enantiomers and a pair of stereoisomers.There are three types of A-ring:cyclopentanone ring,pyrrolidinone and furanone ring.Compound 7 is a kind of aromatic polyketone dimer with novel 6/5/5/6heterotetracyclic ring system.Their planar structures were determined on the basis of 1D and2D NMR,high resolution mass spectrometry（HRESIMS）,and IR data.Their absolute configurations were determined by single crystal X-ray diffraction analysis and ECD calculation.After a variety of activity screening,compounds 2 and 3 exhibited strong PTP1B inhibitory activities with IC₅₀values ranging from 9.4 to 27.3μM.In order to adapt to the ecological environment,the metabolic mechanism of fungi growing in special environments is more complex than of fungi growing in common environment,on this basis,more compounds with novel structures may be produced.Therefore,the secondary metabolites were deserved further research and exploration.The Trichoderma citrinoviride was isolated from a Hainan wetland,in the current study,24compounds were isolated and elucidated,including two new diterpene glycosides（14 and 15）.Compounds 14 and 15 are the first example of harzianone style glycosides,which have a4/5/6/7 four-ring skeleton.To determine the absolute configuration of the mannose of compounds 14 and 15,acid hydrolysis and derivatization were performed,the GC retention times of the derivatives and the standards were compared,which suggested the mannose of compounds 14 and 15 to be D-mannose.