Study On Terpenoids Constituents And Antiviral Activities Of Saussurea Lappa And Croton Tiglium

Since the beginning of the 21 st century,due to reasons such as population mobility,urban population concentration,and changes in lifestyle habits,the human disease spectrum has undergone fundamental changes,and viral infectious diseases have become the main problem of human health and social development.However,the antiviral drugs approved for production and marketing so far,except for amantadine,which is an adamantane compound,are all oligonucleotide derivatives.Clinical antiviral drugs face problems such as a single structure and significant toxic side effects.Based on reverse transcriptase,integrase,protease,glycosidase,Rnase H,and inhibitory activity on viral nucleic acid and viral assembly,structural modification of lead molecules,structural optimization of computer design,structural modification of antisense oligonucleotide,and combinatorial chemistry synthesis are the main research fields for discovering new antiviral drugs.In addition,screening natural antiviral lead compound from plants and microorganisms is also an important direction for developing antiviral drugs.Among them,terpenoids are important skeleton groups of antiviral lead compound.For example,the anti hepatitis B virus activity of the amino acid–sesquiterpene adducts was significantly increased compared with that of the prototype molecule;The heterozygosity of diterpenoids with fatty acids has superior activity against insect borne viruses and HIV viruses compared to the prototype molecules.Therefore,based on the special chromogenic agents and LC-MS analysis guidance,this paper takes the national medicine of Saussurea lappa,which is rich in amino acid–sesquiterpene adducts,and Croton tiglium,which is rich in fatty acid–diterpenoid heterozygotes,as the research object,to find new terpenoid heterozygotes with antiviral activity,and find lead compound for the treatment of viral infectious diseases.In the first chapter of this paper,the research progress on the structure and biological activity of amino acid–sesquiterpene adducts was summarized.So far,a total of 51 amino acid–sesquiterpene adducts from natural sources have been found.The skeleton types involve guaiacane,eudesmane,germacrane and elemene.The amino acid types include proline,aspartic acid and phenylalanine,which have antiviral,anti-tumor,anti-inflammatory and antibacterial biological activities.Most of these heterozygotes exist in compositae plants,and S.lappa is one of the main sources of heterozygotes of them.Six sesquiterpene and amino acid–sesquiterpene adducts have been found in the S.lappa,and they have biological activities such as anti HBV and anti liver cancer.The second chapter of this paper reviews the fatty acid–diterpenoid heterozygotes isolated from C.tiglium and their biological activities.So far,105tigliane-type diterpenoids have been found and identified from C.tiglium,which are characterized by their heterozygous fatty acid molecules at C12,C13 and C20 positions.This kind of heterozygotes have significant antiviral(eg.Zika,HIV,Chikungunya virus),anti-cancer,anti-inflammatory and other activities.The above summary work provides reference and basis for the subsequent research work of S.lappa and C.tiglium.In the third chapter of this paper,the water-soluble components rich in amino acid–sesquiterpene adducts in S.lappa were mainly studied,and the amino acid–sesquiterpene adducts in S.lappa were separated and identified according to the characteristics of mass spectrometry and thin-layer chromatography.A total of 32 compounds were isolated and identified,including two new amino acid–sesquiterpene adducts saussreamines G and H(1 and 2),two new sesquiterpene glycosides saussunosides F and G(3 and 4),and four known amino acid–sesquiterpene adducts saussreamines A,B,C,F(19,6,7,22).The activity test showed that saussreamine B(6)had strong anti HBV activity,and its half inhibition rate of hepatitis B virus surface antigen and e antigen was 11.24 μM(HBs Ag)and 1.25 μM(HBeAg)respectively.In the fourth chapter of this paper,a study was conducted on the fatty acid–diterpenoid heterozygotes in C.tiglium.Through the separation and purification of the petroleum ether extracted part of C.tiglium,17 tigliane-type diterpenoids containing fatty chain substitutions were finally isolated,characterized by heterozygous chain fatty acids such as isobutyric acid,phenylacetic acid,octanoic acid,and nonanoic acid at the C12 and C13 positions of the diterpenoids.Among them,5 are new compounds named 12-O-tiglylphorbol-13-(4Z)-decenoyl(1)、12-O-(2-methyl)butyrylphorbol-13-(4Z)-decenoyl(2)、 12-O-(2-methyl)butyrylphorbol-13-phenylacetate(3)、12-O-tiglylphorbol-13-phenylacetate(4)和 12-O-tiglyl-13-O-phenylacetate-7-oxo-6,7-dihydrophorbol-5-ene(5).At present,the activity test against Zika,HIV and Chikungunya virus is in progress.