SYNTHETIC NUCLEOSIDES AND NUCLEOTIDES .35. SYNTHESIS AND BIOLOGICAL EVALUATIONS OF 5-FLUOROPYRIMIDINE NUCLEOSIDES AND NUCLEOTIDES OF 3-DEOXY-BETA-D-RIBOFURANOSE AND RELATED-COMPOUNDS

yl-2,5-di-O-p-chlorobenzoyl-3-deoxy-D-ribofuranose (1), derived from t he antibiotic cordycepin was coupled with trimethylsilylated derivativ es (2a-c) of N-4-propionylcytosine, N-4-p-toluoyl-5-fluorocytosine and 5-fluorouracil in the presence of trimethylsilyl trifluoromethanesulf onate (TMS-triflate) to give fully acylated nucleosides (3a-b and 3d, respectively), Selective removal of the N-4-propionyl group of 3a by t reatment with hydrazine hydrate gave 2',5'-di-O-p-chlorobenzoyl-3'-deo xycytidine (4). Deamination of 4 with sodium nitrite in trifluoroaceti c acid afforded 2',5'-di-O-p-chlorobenzoyluridine (3c) in good yield, Compounds 3a-d were saponified to give free 3'-deoxycytidine (5a), 5-f luoro-3'-deoxycytidine (5b), 3'-deoxyuridine (5c), and 5-fluoro-3'-deo xyuridine (5d), respectively, These 3'-deoxyribonucleosides (5a-d) wer e then converted to corresponding 5'-monophosphate and further phospho rylated to the 5'-triphosphates by the phosphoroimidazolidate method. The nucleosides (5a-d) were examined for growth-inhibitory effects on mouse leukemic L5178Y cells, and their IC50 values (mu g/ml) were 1.8, 33, 6.5, and 18, respectively. On the other hand, the antiviral activ ities of these compounds on a rhabdovirus, infectious hematopoietic ne crosis virus (IHNV), were moderate (IC50 = 100-500 mu g/ml in CHSE-214 cells), The 5'-triphosphates showed remarkable inhibitory effects on DNA polymerase beta and DNA polymerase alpha-primase purified from tes tes of the cherry salmon, Oncorhynchus masou, but not on common DNA po lymerase alpha from same source.