Synthesis and anticancer activities of novel 5-fluorouracil-1-yl phosphonotripeptides

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 H-1 NMR, P-31 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 alpha-aryl group having a bulky substituent at the ortho-position. Another is the electronic effect of the substituent of the alpha-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.