enter cells by passive diffusion and to revert to FdUMP after removal of the PIV groups by hydrolytic enzymes. The most convenient preparation of PIV2FdUMP was by condensation of 2'-deoxy-5-fluorouridine (FUdR) with PIV2 phosphate in the presence of triphenylphosphine and diethyl azodicarboxylate (the Mitsunobo reagent). PIV2FdUMP was stable in the pH range 1.0-4.0 (t1/2 > 100 h). It was also fairly
合成了2'-脱氧-
5-氟尿苷5'-单
磷酸酯(Fd
UMP)的双[(新戊酰氧基)甲基] [
PIV2]衍
生物,作为Fd
UMP潜在的膜渗透性前药。该化合物设计为通过被动扩散进入细胞,并在通过
水解酶去除
PIV基团后还原为Fd
UMP。最方便的制备
PIV2Fd
UMP的方法是在
三苯基膦和偶氮二
羧酸二
乙酯(Mitsunobo试剂)存在下,将2'-脱氧-
5-氟尿苷(FUdR)与
磷酸PIV2缩合。
PIV2Fd
UMP在1.0-4.0的pH范围内稳定(t1 / 2> 100小时)。在pH 7.4(t1 / 2 = 40.2小时)时也相当稳定。但是,在0.05 M NaOH溶液中,它迅速降解(t1 / 2 <2分钟)。在猪肝羧酸酯酶存在下,将PIV2FdUMP定量转化为单[[(新戊酰氧基)甲基] [PIV1]类似物PIV1FdUMP。孵育24小时后,仅观察到痕量的FdUMP(1-3%),表明PIV1FdUMP是
羧酸酯