Photochemistry of 5‐fluorouracil Analogues, Glycosides and Poly‐fu*

Abstract— 1. The primary photoproduct of 1,3‐dimethyl‐5‐Ruorouracil (DMFu) in aqueous medium is the hydrate, 1,3‐dimethyl‐5‐hydro‐6‐hydroxyhydro‐5‐fluorouracil (DMFu.H2O). 2. When irradiated at wavelengths shorter than 270 mμ, DMFu.H2O in turn eliminates HF, the resulting photoproduct being principally 1,3‐dimethylbarbituric acid. 3. Hence irradiation of DMFu with mercury resonance lamps (254 mμ) leads initially to formation of DMFu.H2O, then to dimethylbarbituric acid, and finally to further products. 4. A similar sequence of reactions prevails on irradiation of DMFu in methanol, the primary photoproduct being DMFuCH3OH; this in turn is transformed by elimination of HF at 254 mμ to 1,3‐dimethyl‐6‐methoxyuracil. 5. At room temperature DMFu.H2O is remarkably stable at neutral and acid pH. At 100° in 1N HCI for 1 hr it is quantitatively converted to DMFu. In alkaline medium (pH˜ 10) about 5–10 per cent reverts to DMFu, the remainder undergoing ring opening. By contrast the methanol addition product eliminates CH3OH to regenerate DMFu in both acid and alkaline media. 6. Both the neutral and anionic forms of 5‐fluorouracil, its glycosides, and poly‐FU exhibit analogous photochemical behaviour. Quantum yields for these have been evaluated in both ordinary and heavy water. 7. It follows that u.v.‐inactivated viruses or infectious RNA, containing incorporated fluorouracil residues, should be susceptible to biological dark reactivation. The extent of such dark reactivation should be greater with increasing wavelengths of irradiation where initial photoproduct formation is limited to the hydrate. Some additional potential biological applications of the results are discussed.