The reagent nitronium tetrafluoroborate in sulfolane was investigated as a nitrating agent for pyrimidine bases, nucleosides, and nucleotides. Reaction of uracil (l), 1-methyluracil (3), or 1,3-dimethyluracil (5) with N02BF4 in sulfolane led to 80-90% yields of the corresponding 5-nitro derivatives, 5-nitrouracil (2), 1-methyl-5-nitrouracil (4), and 1,3-dimethyl-5-nitrouracil (6). Uridine (7) and 2'-deoxyuridine (8) failed to give significant yields of 5-nitro nucleosides, but rather suffered extensive glycoside bond rupture under the conditions employed. However, 2'-deoxyuridine 5'-monophosphate (12) was readily nitrated to give two products that accounted for 70% of the starting material, namely, 5-nitro-2'-deoxyuridine 5'-monophosphate (13) and its 3'-O-nitrate (14). These nucleotides 13 and 14 were dephosphorylated by Escherichia coli alkaline phosphatase t o the corresponding nucleosides, 5-nitro-2'-deoxyuridine (15) and 3'-0,5-dinitro-2'-deoxyuridine (16). In addition, uridine 5'-monophosphate (10) was converted by nitronium tetrafluoroborate/sulfolane to 5-nitrouridine 5'-monophosphate (1 l), which was also prepared by the action of POCl&riethyl phosphate on 5-nitrouridine (9).Pyrimidine nucleosides and nucleotides, substituted a t the 5 position by various functional groups, are of interest for a t least two reasons: first, C-5 substituted nucleosides may possess antiviral and/or antitumor properties;lA second, when incorporated into nucleic acids, the structural modification may provide valuable information for the study of, for instance, t h e physicochemical properties5 and interferon-inducing abilitys of polynucleotides. The nitro group, because of its potent electron-withdrawing properties, would seem a modification of special interest in view of the well-documented antiviral and/or antitumor activities of two deoxyribonucleosides, namely, 5-fluoro-and 5-trifluoromethyl-2'-deoxyuridine.5 5-Nitrouridine was first synthesized by Wempen et al.' who used nitric acid t o nitrate 2',3',5'-tri-0-(3,5-dinitrobenzoyl)-uridine; later, the nucleoside was prepared by the Hg(CN)2 nitromethane condensation procedure.8 Prystas and Sormg found t h a t an analogous nitration approach to a similarly protected 2'-deoxyuridine afforded only glycoside bond cleavage. They did, however, obtain a 1% yield of an anomeric mixture of t h e di-0-toluyl derivative of 5-nitro-2'-deoxyuridine when 5-nitrouracilylmercury was reacted with the protected 2'-deoxy-~-ribofuranosyl chloride. An enzymatic synthesis of 5-nitro-2'-deoxyuridine was reported by Kluepfel e t a1.,I0 but this method cannot be regarded as unambiguous since only UV spectra and elemental analysis were provided to support t h e structure of the product. Additionally, this approach is inconvenient, since large amounts of crude trans-N-deoxyribos ylase from Lactobacillus cultures must be employed. In view of the report by Kluepfel e t al.10 t h a t this enzymatically prepared 5-nitro-2'-deoxyuridine possessed potent antiviral properties, we considered it imperative t ...
