Studies On Synthesis And Application Of Novel Myricetin Derivatives

In this work, the extraction and derivatization processes of myricetin were investigated, followed by the biological evaluation of myricetin and its derivatives as antimicrobial and antioxidant agents.Firstly high-purity myricetin was extracted and separated from Ampelopsis grossedentata by column chromatography and recrystallization, respectively. Base on a comparison with column chromatography, the simple technology, high extraction efficiency, short extracting time, small amount of solvent required and environmental protection of recrystallization method demonstrated its suitability for industrial production.As a natural flavonol, myricetin shows diverse biological activities but its practical application value is limited by its low water solubility and stability. According to the association principle, a series of novel myricetin derivatives (MY-ORn, n=2-7) were synthesized by Williamson ether synthesis. The contents of these derivatives were determinated by TLC and HPLC, while the structures of them were characterised by means of UV, IR, LC-MS, HRESIMS and NMR.Antibacterial activities of myricetin and its derivatives were determined in vitro.When the activities of all the compounds were compared, it was found that MY-OR6 showed the highest antibacterial activity against all the tested sensitive strains followed by MY-OR2 and MY-OR3, whereas MY-OR4 and MY-OR5 were even worse than myricetin, which indicated that the antibacterial activities of novel myricetin derivatives were affected by the number of ethylene glycol units and the length of side chains. The most sensitive bacterial species on these compounds was Staphyloccocus aureus, whose minimal inhibitory concentrations (MIC) was in range of 1.95-62.50 μg/mL. Moreover, MY-OR6 showed antibacterial activity against all the bacterial species with inhibitory concentration of 1.95-31.25 μg/mL.The inhibition effects of myricetin and its novel derivatives on Fusarium oxysporum f.sp.cubense race 4, Rhizoctonia solani (pepper strain) kuhn Schl, Helminthosporium tritici-vulgaris Nishik, Helminthosporium tritici-vulgaris Nishik and Fusarium oxysporum f.sp. Niveum were evaluated by mycelial growth rate method. The results showed that MY-OR^ and MY-OR7 had stronger antifungal potential than other derivatives, even better than the positive methyl thiophanate. It should be noted that MY-OR7 exhibited the best inhibitory activity against S.sclerotiorum (eggplant strain) (Lib) De Bary, giving 50%effective concentration (EC50)of 23.4μg/mL.The antioxidant activities of myricetin and its derivatives were determined by two methods:DPPH and ABTS scavenging activity. The results demonstrated that MY-OR2 and MY-OR6 displayed lower antioxidant activities than myricetin. Regarding the relationship between the chemical structure and the antioxidant activitiy, it has been found that hydroxyl groups in positions 3’,4’,5’mainly influence on antioxidant activity of myricetin.The paper not only lays the theoretical foundation for the further processing of myricetin and its derivatives, but also has great significance for the studies on derivatization and application of other flavonols.