Synthesis And Biological Evaluation Of Quercetin Derivative

This dissertation consists of three chapters:Chapter 1: Flavonoids have been reported to exhibit a wide range of biological effects, including antibacterial, antiviral, ant-inflammatory, antiallergic, and vasodilatory actions. In addition, flavonoids inhibit lipid peroxidation (LPO) platelet aggregation, capillary permeability, fragility, and the activity of enzyme systems including cyclo-oxygenase and lipoxygenase. Quercetin is a representative flavonols, which exists widely in nature as its glycoside derivative. It contains the necessary structure for a flavonol to be active, such as 5, 7 dihydroxy in A ring, 3',4' dihydroxy in B ring, the double bond between C2 and C3, a ketone group at the position C4. Therefore quercetin and its glycoside derivatives have almost all of the activity that flavonols have. Because the natural sources are not suitable for research due to their complicated as well as the difficulty to gain pure preparation from natural products, it is necessary to prepare them by chemosynthesis method. We designed the synthetic route of the target compounds:1. The synthesis of quercetin-3-O-glycosideMethod a. Rutin was be hydrolysis by acid to get quercetin, and then ketal was obtained through selective protection of quercetin with dichlorodiphenylmethane. Ketal is coupled with corresponding acetylglycosyl bromide in DMF/K2CO3 to afford the corresponding blocked glycosides. Cleavage of diphenylmethylene group was performed by catalyzed hydrogenolysis in the presence of 10% Pd/C. Target compound was afforded by removing the acetyl protecting group using CH3OH and CH₃ONa.Method b. Benzylation of rutin and then hydrolysis of the corresponding product afforded 3', 4', 7-O-tribenzylquercetin. The latter condensated with acetylglycosyl bromides in a two-phase system consisting of chloroform-0.25M aqueous potassium carbonate using tetrabutyl ammonium bromide as catalyst to yield the protected glycosides. Cleavage of benzyl group was performed with hydrogenolysis catalyzedby 10% Pd/C. Target compound was afforded by removing the acetyl protecting group using CH3OH and CH3ONa.2. The synthesis of quercetin-3, 7-O-dig]ycosideRutin hydrolysis rutin by acid to get quercetin, and then ketal was obtained through selective protection of quercetin with dichlorodiphenylmethane. Ketal reacted with corresponding acetylglycosyl bromide in a two-phase system consisting of ch3oroform-0.25M aqueous potassium carbonate using tetrabutyl ammonium bromide as catalyst to afford the protected glycosides. Cleavage of diphenylmethylene group was performed by catalyzed hydrogenolysis in the presence of 10% Pd/C. Target compound was afforded by removing the acetyl protecting group using CH3OH and CH3ONa.Eight target compounds were synthesized. Among them, six compounds are natural products. The structure of target compounds was confirmed by IR, ]H-NMR and MS.Chapter 2: To search the flavonoids which possess stronger vasorelaxant activity, a series of quercetin derivatives or analogs have been synthesized and evaluated for vasorelaxant activity in the isolated rat thoracic aorta rings. Most of the tested flavonoids showed concentration dependent relaxant effects against PE-induced contractions in rat aortic rings. These compounds had stronger activity with the augment of logP values.Chapter 3: The development of glycosylation chemistry is reviewed, including the protective groups in glycosidation, the glycosylation methods and the strategies inthe synthesis of oligosaccharides.