Studies On Chemical Constituents And Bioactivities Of Cyathus Stercoreus

The characteristic metabolites in Cyathus are the 5/6/7 tricyclic system of cyathane diterpenoids,which have a wide range of biological activities.And their neurotrophic activity is the most interesting and most promising.To enrich the chemical diversity and bioactivity diversity of metabolites,this thesis systematically studied the secondary metabolites of Cyathus stercoreus based on the OSMAC(One Strain Many Compounds)strategy.We changed the culture conditions and activated the silencing genes of Cyathus stercoreus,new and active secondary metabolites were obtained.This paper has important practical and strategic significance for finding drug lead compounds for the prevention and treatment of neurodegenerative diseases.The main contents are as follows:(1)Eleven fermentation conditions were screened for the target strain,including 9liquid media and 2 solid media.After TLC and HPLC analysis,an optimal culture condition was used to expand the fermentation.(2)We applied a variety of modern chromatographic separation techniques(silica and RP-silica column,Sephadex LH-20,LC-MS,HPLC)and spectroscopy analysis(IR,UV,CD,HRMS,1D/2D-NMR).Seventeen compounds were isolated and identified,including 5 new compounds and 12 known compounds.(3)The obtained new compound was subjected to studies on neurotrophic activity and anti-neuritis activity,and Compounds 1 and 12 showed better activity for promoting axonal growth of PC12 cells,and Compounds 1 and 2 showed better anti-neuritis activity.It provides a realistic basis for the multi-target treatment of lead compounds in neurodegenerative diseases.