Synthesis And Characterization Of Oleanolic Acid Derivatives, And The Study On The Anti-bacterial Activity

Oleanolic acid is a kind of compound of pentacyclic triterpenoids separated fromnatural products, which belongs to the organic triterpenic acid. Widely distributed innature, oleanolic acid is the main functional components of various natural products,with free form existence or with sugar to combine into the glucoside in plants. Thestudy finds that oleanolic acid shows many biological activities, such asanti-inflammatory, anti-tumor, anti-high blood cholesterol, hypoglycemic, anti-HIV,antimalarial, hepatoprotective and many other kinds of pharmacological effects. Theanti-tumor activity of oleanolic acid has been internationally recognized, and it showsstrong cytotoxic activity to tumor cells, which can restrain cancer cells proliferation,invasion and effectively induce apoptosis of cancer cells. It is a good lead compound,which is expected to be the new material of anti-tumor drug candidates.Because oleanolic acid shows a variety of pharmacological activities, lowtoxicity and fewer side effects, a lot of research work has been done on the extraction,content determination and pharmacological activities of oleanolic acid. Meanwhile,oleanolic acid capsule, Zangyinchen capsule and other products have been clinicallyapplied as auxiliary medicine of liver disease. At present, there are more researches onanti-tumor, anti-AIDS, hepatoprotective and other kinds of biological activity of OAderivatives, while the antibacterial activity is fewer at home and abroad. As is knownto all, bacteria and viruses are the main source of infection of infectious diseases,therefore it is very important do relevant antibacterial researches.For further studies about structure activity relationship of oleanolic acid and itsderivatives, this dissertation use oleanolic acid as a lead compound, guided by organicchemical theory and new drug design principle, with the means of organic synthesisreaction method and technology, combined with biological activity test, and doresearches on structure optimization. Also, the research exploits connection piecesglycol which has not been seen in the literature, and test the antibacterial activity ofOA derivatives to obtain new drug candidates with high efficiency and low toxicity.There are three parts in this dissertation：The first part stated the biological activity as well as research progress, clinicalapplication and development prospect of oleanolic acid and listed the development ofantimicrobial agents.The second part can be summarized as follows:(1) The research introduced acetyl groups into ester at C-3of oleanolic acid, andintroduced two carbon linkage at C-28, followed by introducing a series ofcompounds at glycol to form a series of OA derivatives; (2) The research introduced carbonyl group at C-3of oleanolic acid, and introducedtwo carbon linkage at28, followed by introducing a series of compounds at glycolto form a series of OA derivatives.25kinds of OA derivatives were designed and synthesized, and all the structureswere characterized by the methods of IR and1H NMR.23kinds of them were newcompounds.The third part tested the antibacterial activity of the OA derivatives, oxacillin andnorfloxacin were the control material. The eight strains included S.a4220, S.m3065,MRSA3167, MRSA3506, QRSA3505, QRSA3519, E.coli1682and E.coli1356.