5-氟尿嘧啶-1-基磷三肽化合物的合成及抗癌活性研究

Synthesis and Anticancer Activities of Novel 5-Fluorouracil-1-yl Phosphonotripeptides

以 DCC(二环己基碳二酰亚胺 ) /Bt OH(1 -羟基苯并三氮唑 )为偶联剂 ,通过液相偶联法合成了 1 4个新型 5 -氟尿嘧啶 -1 -基磷三肽化合物 ,收率为 5 2 %～ 83 % .所有化合物经 1 H NMR,31 P NMR,IR光谱和元素分析证实 .提出了合成中间体 5 -氟尿嘧啶 -1 -基乙酸的方法 ,其优点是操作简便且产率高 .对部分化合物进行了抗癌活性测试 ,结果表明该类化合物对 HL-60和

A series of novel 5 fluorouracil 1 yl phosphonotripetides were synthesized in yield 52%-83% by peptide coupling reaction with DCC/BtOH as the activiating carboxyl group reagent. All products were characterized by 1H NMR, 31 P NMR, IR spectra and elemental analyses. The facile method was used to synthesize 5 fluorouracil 1 yl acetic acid(an important intermediate). It was found that two main factors affected the conversion of[(5 fluorouracil 1 yl)methylformyl]aminomethylformic acid to the title compounds. One is the apparent steric hindrance of an α aryl group having a bulky substituent at the ortho position. Another is the electronic effect of the substituent of the α aryl groups. The electron withdrawing groups decrease the nucleophilicity of the amino group. The yields of all products containing the strong electron withdrawing groups were lower than those of other products. The in vitro antitumor activity test showed that some of the synthesized compounds are the potential anticancer agent.