SYNTHETIC NUCLEOSIDES AND NUCLEOTIDES. XI. FACILE SYNTHESIS AND ANTITUMOR ACTIVITIES OF VARIOUS 5-FLUOROPYRIMIDINE NUCLEOSIDES

Condensation of 2, 4-bis-trimethylsilyloxy-5-fluoropyrimidine (2a) with 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-D-ribofuranose (3a) by Friedel-Crafts catalysts has been studied. When the reaction was run in acetonitrile at room temperature for 3 hr with 1 : 1 : 1 molar ratio of the base, sugar and stannic chloride, 2', 3', 5'-tri-O-benzoyl-5-fluorouridine (4a) was obtained in an excellent yield (98%). As 1-O-acetyl sugars, 1, 2, 3, 5-tetra-O-acetyl-β-D-ribofuranose (3b), 1, 2, 3, 4, 6-penta-O-acetyl-α-D-glucopyranose (3c), and 1, 2-di-O-acetyl-3-p-toluenesulfonyl-5-O-methoxycarbonyl-D-xylofuranose (3d) could also be used in place of 3a to give the corresponding 1-β-D-glycosyl nucleosides highly stereoselectively. The same method of nucleoside synthesis was extended to the 5-fluorocytosine series to afford 5-fluorocytidine (7a) and 1-β-D-arabinofuranosyl-5-fluorocytosine (7b) in good yields starting from trimethylsilylated N4-acetyl-5-fluorocytosine (6). Additionally, 2, 4-dimethoxy-5-fluoropyrimidine (2b) could be coupled with 3a in similar conditions to give 1-(2, 3, 5-tri-O-benzoyl-β-D-ribofuranosyl)-4-methoxy-5-fluoro-1, 2-dihydropyrimidin-2-one (4e) in good yield. The antitumor activities of the various products obtained against ascites Sarcoma 180 are also described.