Studies On The Synthesis And Bioactivity Of Prenylated Flavonoids And Their Mannich Bases

Prenylated flavonoids exist in many traditional medicinal plants, the presence ofprenylated side chain can increase the lipophilicity of flavonoids, and it is easier topass through the cell membrane in organisms to reach the target role, so flavonoidcompounds modified by prenylated side chain can enhance the biological activity offlavonoids, such as antibacterial, antitumor, anticancer, lowering blood pressure.Flavonoid compounds which are modified by aminomethylation based on Mannichreaction can improve the biological activity of flavonoids and change its physicalproperties. In order to obtain good biological activity drugs, this paper is attempted tosynthesize a series of prenylated flavonoids and Mannich base derivatives from a richsource of raw material naringin, and study their biological activity.1、The natural product8-prenylapigenin was semi-synthesized in the total yield of11%from naringin by reaction steps including glycoside hydrolysis, dehydrogenation,selective methoxy-methylation, O-prenylation, twice Claisen rearrangement undermicrowave irradiation, and deprotection under acidic conditions.2、 The prenylated flavonoids2’-hydroxy-4,4’-dimethoxy-6’-O-isopentenylchalcone (6),2’,6’-dihydroxy-4,4’-dimethoxy-3’-isopentenyl chalcone (7),2’-hydroxy-4,4’-dimethoxy-6’-O-isopentenyl-3’-isopentenylchalcone (8),2’-hydroxy-4,4’-diacetoxy-6’-O-isopentenyl chalcone (10) and4,2’,4’-trihydroxy-6’-O-isopentenyl chalcone (11)were synthesized from naringenin, through selective O-methylation or O-acetylation,O-prenylation, base-catalyzed ring-opening reaction, twice Claisen rearrangementunder microwave irradiation, and the step of deprotection.3、The intermediate5-hydroxy-7,4’-dimethoxy flavonone was synthesized usingnaringin as staring material by the reaction steps including glycoside hydrolysis,selective O-methylation. Then the5-hydroxy-7,4’-dimethoxy flavone (12) wassynthesized through I2/Py dehydrogenation. Then under acid condition and system ofmethanol, fourteen new Mannich base derivatives13~26were synthesized based onMannich reaction using6and12, formaldehyde and secondary amine as the materials,and aminomethylation occurred preferentially at the ortho position of the phenolichydroxyl.4、 All the synthesized Mannich base derivatives were evaluated foracetylcholinesterase (AChE) inhibitory activity by the hydroxylamine ferric chloride method. The results showed that all the Mannich base derivatives except17exhibitedgood AChE inhibitory activity. And the product19(IC50=0.82±0.08μmol·L-1)exhibited better AChE inhibitory activity than the control drug neostigmine mesylate(IC50=1.38±0.12μmol·L-1).5、 Twenty-three prenylated flavonoids and Mannich base derivatives weresynthesized totally in this thesis, and nineteen of them were new compounds. Thestructures of all synthesized compounds have been confirmed by1H NMR,13C NMR,MS, or IR.