DESIGN, SYNTHESIS AND ANTITUMOR ACTIVITY OF PHOSPHOCHOLINE ANALOGS CONTAINING TEGAFUR

AIMTo synthesize the phosphocholine analogs containing tegafur and test their antitumor activity. METHODSN¹-(2-furanidyl)-5-fluorouracil reacted with multimethylene chlorohydrin in the presence of NaHCO₃ in acetonitrile at 80℃ to give N¹-(2-furanidyl)-N³-(hydroxyalkyl)-5-fluorouracil in high yield (≥93%). Its cyclic glycerothiophospholipid conjugate was synthesized by reaction of hexaethylphosphorous triamide, activated by a catalytic amount of iodine, as the phosphorylating reagent with N¹-(2-furanidyl)-N³-(hydroxyalkyl)-5-fluorouracil and 1-O-hexadecyl glycerol as well as sulfur in a one-pot. Cyclic glycerothiophospholipid-nucleosides conjugate readily reacted with triethylamine to give the title compounds. RESULTSNine new compounds (2a～c, 3a～c and 4a～c) have been synthesized. Their structures were confirmed by IR, ¹HNMR, ₁₃CNMR, ₃₁PNMR and elemental analysis. CONCLUSIONThe title compounds (4a～c) showed antitumor activity against human uriaryl bladder cancer cell and more effective than the tegafur.