Total Syntheses And Bioactivities Evaluations Of Three Kinds Of Natural Flavonoids

Flavonoid natural products are widely found in vegetables,fruits,tea,cocoa and other foods.They are the most studied secondary metabolites of plants.At present,more than 8000 kinds of flavonoids have been isolated and identified from plants.Because of their good physiological activities,they are widely used in various nutrition,medicine and cosmetics.However,the content of flavonoids with good physiological activity are often low in plants,so it is difficult to obtain only by isolation and extraction,and it is difficult to get enough amount for further study.By obtaining flavonoid compounds efficiently through artificial synthesis,conducting bioactivity evaluation and exploring the structure-activity relationship,lead compounds that are helpful to the development of food,pharmaceutical and cosmetic industries can be found eventually.In this paper,the total synthesis and activity of three different flavonoids including Isopentenyl flavone(Neocyclomorusin),Furan flavone(Kanjone),Chalone(Velutone F)and their related natural products were studied.The first chapter is the introduction,mainly introduces the basic structure types of flavonoids,flavonoids in antibacterial,anti-inflammatory,antioxidant,antiviral,anti-tumor and other aspects of physiological activities,and expounds the research significance of this paper.In the second chapter,using 2,4,6-trihydroxyacetophenone(2-5)and 2,4-dihydroxybenzoic acid(2-8)as raw materials,four natural isopentenyl flavonoid compounds Neocyclomorusin(2-1),Oxyisocyclointegrin(2-2)and Cudraflavone B(2-3)and Morusin(2-4)were synthesized by esterification,BK-VK rearrangement,C-isopentenylation,cyclization,deprotection and side chain oxidation.Neocyclomorusin(2-1)and Cudraflavone B(2-3)were the first total synthesis.The antibacterial activities of the four natural products were evaluated.The results showed that Cudraflavone B(2-3)and Morusin(2-4)had significant antibacterial activities.The antibacterial activity of Staphylococcus epidermidis and Bacillus subtilis was superior to that of ampicillin.In Chapter 3,nine natural furanoflavones Kanjone(3-1),6-Methoxyisopongaglabol(3-2),6,3’-Dim-thoxy-[2",3":7,8]-Furanoflavone(3-3),2-(3-Hydroxyphenyl)-6-methoxy-4H-furo[2,3-h]chromen-4-one(3-4),Pongol(3-5),6-Hydroxy-3-methoxy-furo[8,7:4",5"]flavone(3-6),Pongamoside B(3-7),Pongamoside A(3-8),Pongamoside C(3-9)were synthesized by three different synthesis methods.The mouse RAW264.7 macrophage inflammation model was established and the anti-inflammatory activity of the nine natural products was evaluated.The results showed that 6-methoxyisopongaglabol(3-2)had the best anti-inflammatory activity with IC50=17.4 μM.In Chapter 4,natural chalketone Velutone F(4-1)and its derivatives 4-2,4-3,4-4,4-5 were synthesized from 1,3-cyclohexadione(4-6)through Friedel-Crafts reaction,Claisen-Schmidt condensation,format reaction and CBS reduction,and their anti-inflammatory activities were evaluated.The anti-inflammatory structure-activity relationship of Velutone F(4-1)was preliminarily investigated by comparing the anti-inflammatory activities of the derivatives.In conclusion,three kinds of natural flavonoid molecules with good biological activities were synthesized in this paper,and their anti-inflammatory and antibacterial activities were preliminarily studied,which laid the foundation for further research and development of these natural products.