Studies On Synthesis Of Bioactivity Polymethoxyfavonoids And Their Glycoconjugates

Polymethoxyflavonoids are highly oxidized and have a low polarity,planar structure of a class of natural flavonoids,with anti-cancer,anti-inflammatory,anti-oxidation and prevention of cardiovascular disease and other pharmacological activity.The activities of natural product ingredients are related to the existence of sugars.During the process of glycosylation,the conformation of the molecule was modified to improve its solubility and orientation,and finally increase its affinity and capacity to biological receptor.In order to develop some new medicinal drugs with higher medicinal value,a series of polymethoxyflavonoids with biological activity and their novel glycoconjugates were synthesized by simple structure modification of them.1.Under alkaline conditions,2-Hydroxy-3,4,5,6-tetramethoxyacetophenone was synthesized by degradation reaction of polymethoxyflavonoids,and 4 kinds of aromatic aldehydes were subjected to aldol condensation reaction to obtain four polymethoxy chalcones.With two methods of I2/DMSO/H2SO4 oxidation and AFO,polyoxylchalerones were subjected to ring-closing reaction to obtain biologically active polyoxoflavones 6?10,in which compound 10 was new.2.With anhydrous potassium carbonate in acetone,compounds 11,13,15 and 17 are reacted with propargyl bromide solution to form the corresponding terminal alkyne compounds 12,14,16 and 18,through nucleophilic substitution reaction.In the CH2Cl2/NaHCO3 two-phase system,the 1,3-dipolar cycloaddition reaction of the terminal alkyne of the compounds 12,14,16 and 18 was carried out by copper catalysis to produce the corresponding 1,4-disubstituted-1,2,3-triazole,in which a series of azide acetylated sugar were synthesized with the raw material of glucose,galactose and lactose,through acetylation,bromination and azide reaction;Finally,twelve novel polymethoxyflavonoid glycoconjugates were obtained uhder the CH3OH/CH3ONa weak base system.This "click chemistry" method is simple,stereoselective specificity,short reaction time and high yield.3.All the synthesized polymethoxyflavonoid glycoconjugates were evaluated for acetylcholinesterase(AChE)inhibitory activity by the Ellman.Test data showed that compounds 16d can certainly enhance the AChE inhibitory activity with an IC50 of 0.202 mmol·L-1.4.The structures of all synthesized compounds have been confirmed by 1H NMR,13C NMR,MS and HRMS.