Synthetic Nucleosides and Nucleotides. XVIII. Synthesis and Cytostatic Activity of 5-Fluoropyrimidine Nucleosides of 3-Amino-3-deoxy-β-D-ribofuranose and Related Compounds

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Treatment of 1,2 : 5,6-di-O-isopropylidene-3-amino-3-deoxy-α-D-allofuranose (1) with trifluoroacetic anhydride afforded crystalline 3-trifluoroacetamido derivative (2) in good yield. Selective removal of the 5,6-O-isopropylidene group of 2 by treatment with 70% acetic acid followed by oxidation with periodate and subsequent reduction with sodium borohydride gave crystalline 1,2-O-isopropylidene-3-deoxy-3-trifluoroacetamido-α-D-ribofuranose (3) in good yield. p-Nitrobenzoylation of 3 followed by acetolysis afforded crystalline 1,2-di-O-acetyl-3-deoxy-3-trifluoroacetamido-5-O-p-nitrobenzoyl-β-D-ribofuranose (5). Coupling of the resulting 1-O-acetyl sugar with bis-trimethylsilylated derivatives of N_4-acyl-5-fluorocytosines, N_4-acylcytosines, 5-fluorouracil and N_4-acetyl-5-methylcytosine using SnCl_4 afforded the corresponding fully acylated nucleosides (7). Saponification of 7 gave 3-amino-3-deoxy-β-D-ribonucleosides (8a-8d). Alternatively, 2,4-dimethoxy-5-methylpyrimidine was also coupled with 5 followed by treatment with ammonia to give 8d. The nucleosides (8a-8d) thus obtained were examined for cytostatic effect on mouse leukemic L5178Y cells. The compounds tested were active against this system and their ED_<50> values were 0.7 μg/ml, 7 μg/ml, 16 μg/ml and 60 μg/ml, respectively.
公益社団法人日本薬学会の論文
1981-10-25