Abstract: Aseries 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, ³¹P NMR, IRspectra 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.

Key words: Fluorouracil, Peptide coupling, Phosphonotripeptides, Anticancer activity