Abstract
Several 4′-thio-2′-deoxypyrimidine nucleosides were synthesized from 2-deoxy-D-ribose via 7 steps. The 4′-thionucleosides were obtained by reaction of the corresponding trimethylsilylated pyrimidine bases with 4-thiosugar(6), which has been synthesized in one step by treatment of 3,5-di-O-benzyl-2-deoxy-D-ribose dibenzyldithioacetal(4) with the Ph3P-I2-Im system. The chemical stability of 4′-thio-2′-deoxythymidine is also described. 5-Fluoro-2′-deoxyuridine (5-FDUR), 5-iodo-2′-deoxyuridine(5-IDUR) and their 4′-thio-analogs 8b, 8c were evaluated for antitumor activity. 5-Fluoro-4′-thio-2′-deoxyuridine(8b) was more inhibitory than 5-FDUR, especially at a concentration of lug/ml.