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.