Isolation Of Chemical Consitituents From Xanthium Italicum Moretti And Synthesis Of Their Derivatives

Natural products have been the important sources for the discovery and design of medicine and pesticide due to the varieties of structure.Xanthium plays an important role intraditional Chinese medicine,of which dried fruit is mostly used There are four main species of Xanthium L in Xinjiang,including Xanthium sibiricum Part,Xanthium italicum Moretti,Xanthium spinosum Linn and Xanthium mongolicum Kitag.Among them,X.italicum,a major invasive species,has become one of the major farmland weeds in Xinjiang due to its strong ecological adaptability and large biomass,and,which has seriously reduced the crop yields.Therefore,the research on the chemical composition and biological activity of X.is of great significance to reveal the basis of its active substances and explore the plant resources.In this study,the chemical components of X.italicum was studied with bioactivity-guided isolation.The derivatives were synthesized according to the optimum lead structure.The main study is as follows:(1)Bioactivity-guided isolation of Xanthium italicum..Bioactivity-guided isolation was carried out through the extraction,separation and structural characterization of the chemical constituents of X.italicum.First,the ultrasonic-assisted method was used to extract the X.italicum.After concentration to obtain the extract,it was subjected to gradient extraction with petroleum ether,chloroform,and ethyl acetate.The petroleum ether phase(PE-fr)and chloroform phase(TCM-fr)were obtained,Ethyl acetate phase(EAC-fr).The MTT method was used to screen the tumor activity outside the antibody for each phase.It was found that the chloroform phase and petroleum ether phase could significantly inhibit the growth of tumor cells.Based on this,this article was further separated and purified,and 16 compounds were finally identified.including four sesquiterpenoids,five triterpenes,one coumarin,one flavonoid,one anthraquinone and organicacids were yielded,xanthatin(1)、xanthinosin(2)、1α,5α-Epoxyxanthatin(3)、Deacetylxanthanol(4)、Lasidiol p-methoxybenzoate(5)、lupeol(6)、α-Spinasterol(7)、Betulin(8)、oleanolic acid(9),betulinic acid(10)、Scopoletin(11)、emodin(12)、quercetin(13)、oleic acid(14)、methyl hexadecanoate(15)、triacontanol(1 6).At the same time,high-performance liquid chromatography(HPLC)was used in this paper.with xanthatin(1)and betulinic acid(10)as the standard substances,The chemical composition of the extracted phases of X.italicum was studied.(2)Study on antitumor and fungicidal activity of X.italicum.MTT method was applied to study the antitumor activity of crude extracts,various extraction phases and related chemical components of X.italicum in vitro.It was found that chloroform phase and petroleum ether had the best activity against liver cancer cells HepG2 and lung cancer cells A549,with inhibition rates of 80%and 50%,respectively.From 16 monomer compounds,six compounds with antitumor activity,such as xanthatin and betulinic acid,were screened out.Among them,the compound with the best inhibitory effect was xanthatin.Its IC50 reached 13.2 μM and 11.3 μM.The inhibitory activity of four pathogenic fungi including Botrytis cinerea,Alternaria solani,Fusarium Oxysporum,and Alternaria alternata was evaluated by the mycelial growth inhibition method.It was found that the chloroform phase had the best antifungal activity,and the inhibition rates of the four plant pathogenic fungi reached above 50%,and their half maximum effect concentrations EC50 were 788.36 μg·mL-1、566.93 μg·mL-1、496.48 μg·mL-1 and 339.39 μg·mL-1.(3)Design and synthesis of derivatives.Based on the structure xanthatin,the design and synthesis of xanthatin anologs was carried out with 3-furoic acid and β-alanine as raw materials,3(furan-3-carboxamido)propionic acid is prepared by acylation,esterification,condensation,ester hydrolysis,etc.,using methanesulfonic acid and P2O5 as The cyclizing agent successfully constructed the[5,7]parallel ring structure.Three kinds of[5,7]cyclic ring derivatives were designed and synthesized using 3-furoic acid and different amino acids as raw materials.