生物活性多甲氧基黄酮羧酸和氨基酸衍生物的合成及其结构表征

Synthesis and Structure Characterization of Bioactive Polymethoxy Flavonoids Carboxylic Acid and Amino Acids Derivatives

多甲氧基黄酮(PMFs)是一类存在于柑橘属植物中具有显著抗癌、抗炎和抗氧化等生物活性的天然产物。为了提高多甲氧基黄酮类化合物的水溶性和药用价值,以2种来源丰富且抗癌活性高的多甲氧基黄酮橘皮素和川陈皮素为底物,分别经过氧丙酮氧化得到多甲氧基黄酮醇[3-羟基橘皮素(7)和3-羟基川陈皮素(8)],化合物7和化合物8分别在K2CO3和N,N-二甲基甲酰胺条件下与氯乙酸乙酯进行Williamson反应,生成了多甲氧基黄酮羧酸酯类衍生物,再经碱性水解合成了2种未见文献报道的多甲氧基黄酮羧酸衍生物[橘皮素-3-O-乙酸(1)和川陈皮素-3-O-乙酸(2)]。化合物1和化合物2在CH2Cl2作溶剂、1-(3-二甲基丙胺)-3-乙基碳二亚胺盐酸盐为缩合剂和4-N,N-二甲氨基吡啶为辅助剂的条件下,分别与2种不同的氨基酸甲酯盐酸盐发生缩合反应,得橘皮素和川陈皮素的氨基酸甲酯衍生物,然后经水解反应得到了4种新型多甲氧基黄酮氨基酸衍生物3~6。对所合成的化合物用1H NMR、13C NMR和MS等方法进行了结构表征。

Polymethoxy flavonoids(PMFs)are a class natural products,which almost exclusively exist in citrus plants possessing distinguished anti-carcinogenic,anti-inflammatory and antioxidative activities.In order to increase the water solubility and medicinal value of PMFs,tangeretin and nobiletin,the two most abundant source and the highest anticancer activity of natural polymethoxy flavonoids,were oxidated by dimethyldioxirane to polymethoxy flavonoids(3-hydroxytangerine(7)and 3-hydroxynobiletin(8)).The compound 7 or 8 was reacted with ethyl chloroacetate by Williamson synthesis in anhydrous potassium carbonate and N,N-dimethylformamide.Then the reaction solution was controlled under alkaline conditions at room temperature for hydrolysis to obtain two polymethoxy flavonoids carboxylic acid derivatives(tangerine-3-O-acetic acid(1)and nobiletin-3-O-acetic acid(2))that have not been reported in the literature.Under the conditions of CH2Cl2 as solvent,EDCI and DMAP as the catalytic system,tangerine and nobiletin carboxylic acid derivatives were reacted with glycine methyl ester hydrochloride and phenylalanine methyl ester hydrochloride respectively and four polymethoxy flavonoids amino acid methyl ester derivative were obtained.After the hydrolysis treatment,four new polymethoxy flavonoids amino acid derivatives 3 to 6 were first synthesized.The structure of all synthesized compounds were characterized by 1H NMR,13C NMR,and MS.