Studies On The Synthesis Of Natural Prenylated Chalcones Xanthohumol And Mannich Bases Derivatives

Chalcones,belong to a class of natural flavonoids with the basic structure of 1,3-allyldiphenylketone,widely exist in a variety of medicinal plants such as safflower,angelica keiskei,licorice.Chalcone derivatives have large flexible,different receptor and extensive biological activities because of the structure of?,?ketene,such as anti-cancer,anti-inflammatory,anti-allergic and so on.Studies have shown that we can improve the biological activity of chalcone derivatives by structure modification,and prenylated group is one of the most important active groups,chalcone derivatives with prenylated structure unit have stronger biological activity,therefore the synthesis of xanthohumol is some big hot spots of research in recent years.In addition,we can increase the hydrophilicity in the human body by the intro duction of nitrogen polar groups on the molecular structure,and the Mannich reaction is an organic synthesis method to use widely,the introduction of nitrogen-containing polar groups by the Mannich reaction of chalcone can both increase the biological an d pharmacological activity of chalcone and increase its water solubility.To develop pharmaceutical precursors with higher medicinal value,a series of biologically active prenylated chalcone and its Mannich base derivatives were synthesized using phlorogl ucinol,hesperetin and naringenin as raw materials.1.2,4-Dimethoxymethyl-6-hydroxyacetophenonewassynthesizedvia Friedel-Crafts acetylization and selective O-methoxymethyl,with phloroglucinol as starting compound.4-Methoxymethylbenzaldehyde was synthesized through selective O-methoxymethylwithP-hydroxybenzaldehydeasstartingcompound.2',4,4'-Trimethoxymethyl-6'-hydroxychalcone?1?was synthesized through the Claisen-Schmide condensation reaction between 2,4-dimethoxymethyl-6-hydroxyace-tophenone and 4-methoxymethylbenzaldehyde.A series of prenylated chalcone compounds 2,3,4 and xanthohumol 5 was synthesized through O-prenylation,Florisil catalyzed isopentenyl rearrangement,O-methylation with dimethyl sulfate,taking off the protection base with compound?1?as substrate.2.3',4',7-Trimethoxy-5-hydroxydihydrogenflavonoids?6?and4',7-dimethoxy-5-hydroxy dihydrogen flavonoids?12?were synthesized from hesperidin and naringenin through O-methylation with dimethyl sulfate.Then,a series of prenylated chalcone compounds 7,8,9 and 13,14,15 were synthesized through O-prenylation and ring-opening reaction under weak base potassium carbonate catalysis,Florisil catalyzed isopentenyl rearrangement,with compounds?6?and?12?as substrates.3.Thirteen new prenylated chalcone Mannich base derivatives 10a-10e and11a-11h were synthesized based on Mannich reaction under the hydrochloric acid catalytic,with xanthohumol?5?and 2'-hydroxy-3,4,4'-trimethoxy-6'-O-isopentenyl chalcone?7?as the substrate,methanol as solvent,formaldehyde and secondary amines as the materials,and aminomethylation modification occurred its 5'position and 3'position.The structure of all synthesized compounds have been confirmed by ¹H NMR,¹³C NMR and MS.4.The antiproliferative activities of target compounds were tested in vitro on a panel of three human cancer cell lines?Hela,HCC1954 and SK-OV-3?by CCK-8assay.The results showed that xanthohumol?5?exhibit more potency in the antiproliferative activity against all the three cancer cell lines with IC₅₀0 values were9.851,5.449,4.518?M as compared to positive control cis-Platin?...