Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

Methyl 2,3-O-isopropylidene-D-ribofuranoside (IV) was alkylated with alkyl halides in the presence of sodium hydride and the products were transformed by acid hydrolysis and glycosylation into methyl 5-O-alkyl-D-ribofuranosides VII. Benzoylation of VII followed by acetolysis afforded 1-O-acetyl-2,3-di-O-benzoyl-5-O-alkyl-D-ribofuranoses IX which on reaction with 2,4-bis(trimethylsilyloxy)pyrimidine in the presence of tin tetrachloride in acetonitrile and subsequent hydrolysis gave 5'-O-alkyl-2',3'-di-O-benzoyluridines XIa-XIe. Methanolysis of compounds XI furnished 5'-O-alkyluridines III. The 5-O-allyl derivative XII was hydroxylated in the presence OsO₄ and transformed further to 5'-O-(RS)-(2,3-dihydroxypropyl)uridine (IIIg) and its tetrabenzoate XVI. Compounds XI and XVI on reaction with elemental fluorine in acetic acid afforded benzoyl derivatives of 5'-O-alkyl-5-fluorouridines XVIIa-XVIIe and XIX which were methanolyzed to give 5'-O-alkyl-5-fluorouridines II. This procedure afforded 5'-O-methyl (IIa), ethyl (IIb), n-butyl (IIc), n-hexyl (IId), n-octyl (IIe), and (RS)-(2,3-dihydroxypropyl) (IIf) derivatives of 5-fluorouridine. None of the compounds II exhibited antibacterial effect on Escherichia coli B or antiviral activity against HSV-1, HSV-2, vaccinia virus or vesicular stomatitis viruses. Compounds IIc,d,e suppressed the growth of L 1210 mice leukemic cells at concentrations of 10^-5 to 10^-6 mol l^-1; the 5'-O-n-butyl derivative IIc has the highest activity (ID₅₀ 2·8 μmol l^-1) but does not prolong the life span of L 1210 leukemia bearing mice following repeated daily doses of 80 mg/kg.