5-氟尿嘧啶甘氨酸类化合物的合成、表征及抗癌活性

常温下,以5-氟尿嘧啶为起始原料,以1-乙基-3-(3-二甲氨基丙基)碳二亚胺(EDCI)和1-羟基苯并三氮唑(HOBt)为缩合剂,通过液相偶联法,合成了2-(5-氟尿嘧啶-1-基乙酰基)氨基乙酸甲酯,收率72%;控制pH=10～11,温度20～30℃水解得到相应的2-(5-氟尿嘧啶-1-基乙酰基)氨基乙酸,收率75%。两个化合物的结构通过1HNMR、13CNMR、MS、IR确证;通过紫外吸收光谱初步揭示了化合物的抗肿瘤机制;委托国家新药筛选中心进行了体外抗白血病细胞株HL-60和肝癌细胞株BEL-7402活性测试,结果表明,该化合物具有一定的体外抑制肿瘤作用。

Synthesis, Characterization and Antitumor Activities of Glycine Derivatives Containing 5-Fluorouracil

Methyl 2-(5-fluorouracil-1-yl) acetamidoactate was synthesized at room temperature by liquid coupling method with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDCI) with 1-hydroxybenzotriazole(HOBt) as condensation reagent,and 5-fluorouracil as initiating material,in which the yield was 72%.2-(5-Fluorouracil-1-yl)acetamidoactic acid was obtained by hydrolysis under a controlled condition of pH 10～11 and 20～30 ℃ with a yield of 75%.The structures of the two compounds were characterized by method of 1HNMR,13CNMR,mass spectroscopy and infrared spectroscopy etc.The antitumor mechanism of the compounds was initially revealed by UV spectra.The compounds′ in vitro antitumor activity against HL-60 and BEL-7402 was tested by the National Center for Drug Screening.The results indicate that the compounds have certain antitumor effect in vitro.