Studies On The Chemical Constituents Of Four Higher Fungi And The Synthesis Of Andrographolide-Imidazolium Salts

Natural products provid rich types of chemical structures to the development of drug discovery. Based on leading compounds, combined with the relationship between structure and biological activity and metabolism studies, scientists have conducted the further research on structural modification and synthetic analogs of natural compounds to improve the efficacy and reduce toxicity, which can be derived a series of new drugs from one effective leading natural compound. This is an important way for drug discovery, and people have achieved fruitful results. In the contemporary drug discovery, natural products is the most important source of development of new drugs which can not be replaced.This dissertation is composed of six chapters.In chapter one, the chemical structures and biological activities of naturally occurring sesquiterpenes from higher fungi were reviewed.From chapter two to chapter five, chemical investigation on four higher fungi, including Fomes fomentarius, Agaricus arvensis, Coprinus plicatilis and Daedaleopsis tricolor, was comprehensively studied.Seventy-one compounds, including twenty-one new ones (two new skeleton sesquiterpenes), were isolated from the above mentioned species. Their structures were established on the basis of extensive spectroscopic methods in combination with single-crystal X-ray diffraction analysis. The types of structures amoung the compounds included benzene derivatives, cyclopeptides, steroids, sesquiterpenes, diterpenes, triterpenes, nucleosides, tetrahydrofuran derivatives and fatty acids and so on. Some of the isolated compounds were evaluated for antimicrobial or cytotoxic activity.Three new phenyl-ethanediols were isolated from the fruiting bodies of the mushroom F. fomentarius, and the compounds showed weak antimicrobial activity.Two new drimane sesquiterpenoids were isolated from cultures of the basidiomycete A. arvensis.A new cyclic dipeptide were isolated from cultures of the basidiomycete C. plicatilis.The chemical constituents of cultures of D. tricolor were investigated, which led to the isolation of two new skeleton sesquiterpenes, seven new bisabolane sesquiterpenoids (including three γ-lactams and four nor-sesquiterpenoids), a cadinane sesquiterpene, a heptanorergosterane derivative, a ribopyranoside, a furan derivative, and two chain polyols.In chapter six, a new series of andrographolide-imidazole hybrid compounds and their imidazolium salts (forty-six new compounds) were designed and synthesized. The biological activities of these compounds are studying.