Studies On Synthesis Of New Flavonols As Well As Its Glycoside Or Vinyl Ether Derivatives

Flavonoids are widely found in nature, with a rich source of biological activity diversity. But the active ingredients in natural medicines in low and coexist with the shortcomings of activity and toxicity, therefore it can not meet the needs of human life and research. So, through chemical synthesis and biological method for the synthesis of new flavonoids and their derivatives is a significant and important research.1, Start with a simple material resorcinol, phloroglucinol, 3,4,5–trimethoxy- benzaldehyde, after F-C acylation, Darkin reaction, methoxy reaction, Fries rearrangement, aldehyde ketone condensation reaction, AFO reaction, I2 dehydrogenation reaction, Pd/C reduction reaction, We get 3',4',7-trimethoxyflavone alcohol 1, 3',4'-bisbenzyloxy-7-methoxy- flavonol 2, 3',4',5,7- tetramethoxy flavonol 3, 3',4'-dihydroxy -5,6,7-trimethoxy flavonol 4. And the compound 4 is a new flavonol. The results showed that, when A ring has methoxy substituent in 5-position, the AFO reaction of chalcone gets aurones and dihydroflavonols or other side products, while the A ring has no substituent in 5-position, there is no side products generated, but B ring substituents have no influence on the reaction.2, The flavonol 3-O-glucoside bit easier with isopentenyl or farnesene or glycoside donor, and flavonoid glycosides increase the base of the hydrophilic, allyl ether of flavonoids improve the base of the hydrophilic properties, while flavonoids ether improve the lipophilic properties. Choose flavonol 1 for flavonol glucoside, galactoside, galactoside and isopentenyl, farnesene ether modification. All the raw sugar hydroxyl by acetylation and the anomeric carbon with bromine donor glycosides were prepared, and then K2CO3/acetone system for glycosylation substitution reaction, and then ammonia/methanol system for remove the off-acetyl substituents, them we get glycosides substituted flavonols 8~13 which have not been reported. And by the substitution reaction, we get two allyl ether derivatives 14~15 which have not been reported. These synthesis methods is simple, no side products generation, and suitable for industrial production3, Choose a part of the synthesized compounds for biological activity determination. using MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetra zolium- romide] method to test the compounds 1, 8~15 of tumor cell activity, in order to find biologically active substances. The experimental results show that compound 10 on the A-549 (lung cancer), SMMC-7721 (liver cells), MCF-7 (breast cancer), SW480 (colon cancer cells) have a certain cytotoxicity, IC50 (μM) values are 15.48, 9.7, 14.40, 14.77 respectively, and from the data, it has a strong inhibition to A-549 (lung cancer), other compounds of these cells without apparent toxicity.All of the synthesized compounds have been confirmed by mass spectrometry (MS), infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (1H NMR).