替加氟的硒代卵磷脂类化合物的合成与抗癌活性

Synthesis and antitumor activity of selenophosphocholine analogues containing tegafur

目的合成硒代卵磷脂类似物作载体的替加氟磷脂缀合物,并测定其活性。方法以六乙基亚磷酰三胺作磷酰化试剂,与羟烷基替加氟、1-十六烷基甘油及硒作用,经“一锅法”得到环甘油硒代磷脂替加氟缀合物,通过三乙胺开环得到目标产物。结果得到6个新化合物,其结构经过1H NMR,31P NMR及元素分析确证。结论三乙胺对环甘油硒代磷脂替加氟缀合物开环在室温下2 h完成。反式开环产物对膀胱癌细胞PGA1的抑制作用比原药替加氟强。

Aim To synthesize the selenophosphocholine analogues containing tegafur and test their antitumor activities. Methods The cyclic glyeeroselenophospholopid conjugate of tegafur was synthesized by the reaction of hexaethylphosphorous triamide with N1 -（2-furanidyl）-N3-（hydroxyalkyl）-5-fluyorouraeil and 1-O-hexadeeyl glycerol as well as selenium in one-pot. Cyclic glyeeroselenophospholopid conjugate of tegafur reacted with triethylamine to give title compounds. Results Six new compounds have been synthesized. Their structures were confirmed by 1H NMR, 13p NMR and elemental analysis. Antitumor activity of the title compounds against PGA; was tested. Conclusion The reaction of triethylamine with cyclic glyeeroselenophospholopid conjugate of tegafur very readily occurred, which was finished within 2 h at room temperature. The opening-ring products of trans isomers showed antimutor activity against human uriaryl bladder cancer cell more effective than that of the tegafur.