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

Oleanolic acid and glycyrrhetinic acid are both pentacyclic triterpenoidcompounds. They have similar structure and distribute in nature widely. They haveshown many biological activities, such as anti-bacterial, anti-inflammatory, antiviral,anti-tumor etc. Because of their wide range of biological activities and low toxicity,scientists have done many researches on oleanolic acid and glycyrrhetinic acid abouttheir extraction, determination and pharmacological activities and have many relatedarticles. But articles about their anti-bacterial activity are less.In order to study the structure activity relationship of oleanolic acid andglycyrrhetinic acid and their derivatives in depth, we use them as lead compounds anddo some appropriate modification based on the theories, methods and technology ofpharmaceutical synthesis and organic chemistry. We also do some tests of theirantibacterial activities in order to obtain high efficiency, low toxicity derivatives ofoleanolic acid and glycyrrhetinic acid.There are three parts in this dissertation.First part: Briefly introduce the research progress of antimicrobial drugs.Describe the pharmacological effects, clinical application and development prospectsof oleanolic acid and glycyrrhetinic acid.Second part: Design and synthesize the derivatives of oleanolic acid andglycyrrhetinic acid.(1)Through structure modification of OA at C-2, C-3and C-28,we introduced morpholine to oleanolic acid by epoxide intermediate.(2)We alsointroduced some amino acid and cyclic compounds to oleanolic acid andglycyrrhetinic acid by succinic anhydride linkage.(3)The efficacy could be obviouslyimproved by introducing fluorine to one key position of the drugs. So we designed tointroduce fluorine to oleanolic acid and glycyrrhetinic acid. Through a series ofreactions, we successfully introduced parafluorobenzoic acid. Finally we synthesized19derivatives of oleanolic acid and8derivatives of glycyrrhetinic acid by5schemes.All the structures were characterized by the methods of IR and1H NMR. There are20kinds of the compounds have not been reported.Third part: The antibacterial activity test. We tested the oleanolic acid andglycyrrhetinic acid and their derivatives through9kinds of bacterial strains. Theresults showed that compound O-9had better antibacterial activity.