Studies On The Semisynthesis Of Bioactive Lfavonol And Their Glycoconjugates From Hesperidin

The flavonoids are widely found in nature which possess extensive biologicalactivities and pharmacological properties.They mainly include flavone, flavonol andflavanone. To regard as one of the important natural products and the main activeingredient of medicinal plants, they widely exist in citrus. Because of their specialchemical structure, they have many important physiological functions in mammalsand other types of cells, they also have therapeutic effects on many human diseases,including inhibition of enzyme activity, antivascular-disease activity, antiinfectiveactivity, anticarcinogenic activity, antiviral activity and antioxidant effect. There aremany reactive sites in the structure of flavonoids, thus the flavonoids have highchemical reactivity. The thesis aims at the studies on the semisynthesis of flavanoneand new flavonol glycoconjugates from hesperidin.1. A series of natural flavonol compounds were synthesized by the DMDOmethod, they were7,5,3’,4’-tetra methoxy flavonol,3-hydroxyl-4′-methoxy-5,7,3′-three benzyl flavonol and4′-methoxy-7,4’,5-threehydroxyl flavonol.Through the following steps, including removing glycosyl fromhesperidin in acidic conditions, the dehydrogenation of iodine/pyridine, themethylation of hydroxyl, the benzylation of hydroxyl, the oxidation of acetone andthe removal of benzyl, we acquired a variety of natural flavonol compounds. Byresearching several methods of synthesis of flavonol compounds, the results showedthat AFO reaction method was applicable to the synthesis of flavonoids which had nosubstituents or had the smaller volume substituents on C-5site. Otherwise, theproduct would be aurones. So we finally synthesized the flavonols which containedbig volume substituents on C-5site with DMDO method. Through the oxidation ofacetone, we got one intermediate which had a three-membered ring that containedoxygen. Ultimately, we got flavonol compound1,2and3by the ring openingreaction.2. Using flavonol compound7,5,3’,4’-tetra methoxy flavonol and3-hydroxyl-4′-methoxy-5,7,3′-three benzyl flavonol as precursors to link glucosidecompounds by “click chemisty”, we got a series of flavonol glycoconjugates. Byusing “click chemisty” method in which there was a1,3-dipolar cycloadditionreaction between the terminal alkyne and the azide group of azide glucoside compounds, we efficiently synthesized a series of flavonol glycoconjugate compounds6-25.3. The structures of the synthesized compounds have been confirmed by~1H NMR,MS and IR.3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT)colorimetric method are applied to the antitumor activity of flavonol glycoconjugatesthat synthesis before in vitro test. Selected the leukemia cell line, hepatocellularcarcinoma cell line, lung cancer cell lines, breast cancer cell lines and colon cancercell line as target cells, the results showed that compound11could inhibit the growthof tumors of the breast cancer cell lines and the leukemia cell line.