Reaction of perbenzoylated aldopentafuranosyl derivatives of uracil with fluorine in acetic acid afforded perbenzoylated 5-fluorouracil nucleosides. Their methanolysis gave the following free nucleosides of 5-fluorouracil: β-D-ribofuranoside (Id), 2-deoxy-β-D-ribofuranoside (IId), their enantiomers VIII and IX, α-D-ribofuranoside (XIII), 2-deoxy-α-D-ribofuranoside (XV), β-D-arabinofuranoside (IV) and its L-enantiomer X, β-D-xylofuranoside (V) and its α-D-anomer XI, α-L-lyxofuranoside (VI) and 2-deoxy-α-L-lyxofuranoside (VII) and the enantiomers of the latter two compounds, XII and XIV, respectively. Analogously were obtained 5-deoxy-β-D-ribofuranoside (III), β-D-ribopyranoside (XVI) and 1-(S)-(2,3-dihydroxypropyl)-5-fluorouracil (XVIIc). 1-Allyl-5-fluorouracil (XVIII) was prepared by reaction of allyl bromide with 2,4-bis(trimethylsilyloxy)-5-fluoropyrimidine. The cell-free extract from Escherichia coli cleaves all the 5-fluorouracil nucleosides in which the nucleoside carbon atom has the R-configuration and the 3'-hydroxyl of the sugar moiety is in trans-relation to the base. Compounds which have not these structural features are resistant. Besides nucleosides which on enzymatic cleavage afford 5-fluorouracil, also the non-cleavable 1-(2-deoxy-β-L-ribofuranosyl)-5-fluorouracil (IX), 1-(2-deoxy-α-D-ribofuranosyl)-5-fluorouracil (XV) and 1-(2-deoxy-α-D-lyxofuranosyl)-5-fluorouracil (XIV) exhibit an antibacterial effect towards E. coli (ID50 1.0-2.5 . 10-5 M). This effect can be reversed by 2'-deoxyuridine but not by thymidine.
A New Method of the Introduction of CF3‐ and C2F5‐Groups into Pyrimidine Derivatives and their Antiherpes Activity
A new method of the perfluoroalkylation of uracil derivatives is described. The irradiation of aqueous solutions of uracil and uracilnucleosides with bis‐(perfluoroalkyl) mercury (CnF2n+1)2Hg n = 1, 2 under the exclusion of oxygen in the presence of catalytic amounts of azo‐bis‐isobutyronitril at 254 nm for several hours gave new 5‐perfluoroalkylated compounds. In this way we obtained 5‐trifluoromethyluracil (5a), 5‐pentafluoroethyluracil (5b), 5‐trifluoromethyl‐2′‐deoxyuridine (6a), 5‐pentafluoroethyl‐2′‐deoxyuridine (6b) and 1‐(ß‐D‐arabinofuranosyl)‐5‐trifluoromethyluracil (7a) in different yields. The perfluoroalkylated compounds were tested against HSV‐1 and HSV‐2 viruses on human lungefibroblasts. The compounds are markedly less potent than other known nonfluorinated compounds.
Syntheses of 1‐(β‐D‐Arbinofuranosyl)‐pyrimidines
New synthetic methods of 1‐(β‐D‐arabinofuranosyl)‐pyrimidines are described. 1‐(β‐D‐arabinofuranosyl)‐uracil, 1‐(β‐D‐arabinofuranosyl)‐5‐fluorouracil, 1‐(β‐D‐arabinofuranosyl)‐thymine, and 1‐(β‐D‐arabinofuranosyl)‐cytosine can be obtained in a high yield by the splitting of the anhydrobond in 2,2′‐anhydropyrimidines in dipolar aprotic solvents, such as HMPT, DMF, and DMSO, respectively, in the presence of activated elemental copper.
Unlike the formation of cyclopyrimidiens ribonucleosides are directly transformed to the corresponding arabinofuranosyl derivatives by the reaction with diphenylcarbonate and NaHCO3 in the presence of copper. The reaction proceeds probably via an intermediate formation of the cycloproduct. Further aspects on the mechanism are described.
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