Uracil glycol

Irradiation of air-free solutions of pyrimidines can give products resembling some of those produced by ultraviolet light, but probably by a quite different mechanism. Irradiation of 1,3-dimethyluracil with 200 kV X-rays produces not only the expected 5,6-glycol, but also 6-hydroxyl-l,3-dimethyl-5-hydrouracil, the same isomer as the UV-produced hydrate discussed elsewhere in this chapter. The yield of the hydroxy compound is low, G = 0.35 molecules/100 eV absorbed. Cytosine glycol is formed in gamma-irradiated cytosine solutions, and this deaminates completely to the uracil glycol. These products are probably formed by addition of an OH to the 6-position of the pyrimidine and then dismutation of hydroxy radical. The major products formed in the radiolysis of air-free solutions of pyrimidines or purines have not yet been identified. 

Dihydroxy-5,6-dihydrouracil, uracil glycol (also in nucleosides, nucleotides and DNA) Uridine-5 -phosphate... 

The tautomeric properties of 5,6-dihydroxyuracil, uracil glycol (99JST(459)1) and thymine glycol (98JCS(F)1813) were characterized using ab initio methods. The 2,4-diketo tautomeric form was found to be the most stable for all these compounds in both polar and non-polar solvents. 2-Oxo-4-hydroxy tautomers were found to be more stable than 2-hydroxy-4-oxo tautomers for uracil derivatives, whereas the opposite trend was reported for thymine glycol. 

For unsubstitUted or lower alkylated dioxotriazines, it is advantageous to cyclize semicarbazones by sodium ethylate in ethylene glycol as described by Chang and XJlbricht. In this reaction 6-aza-uracil is obtained in 66% yield. The procedure was used for the preparation of labeled 6-azauracil ° and later for the synthesis of a number of 6-alkyl derivatives including 6-azathymine. °... 

The pyrimido[6,l-F][l,4]oxazine-6,8-diones 164 (Y = O) and pyrimido[6,l-c][l,4]thiazine-6,8-diones 164 (Y = S) were synthesized by treating 6-chloromethyl-uracil with methyl glycolate 162 (Y = O) or methyl thioglycolate 162 (Y = S), respectively, and reacting the resulting 163 with DMF-dimethyl acetal (Scheme 20) <2004W02004/014354>. 

The template polymerization was carried out at GO C in dimethyl sulfoxide/ethylene glycol mixture using AIBN as radical initiator. It was found that under these conditions interaction between adenine and uracil groups is remarkable. 

Huttermann J, Ward JF, Myers LS Jr (1971) Electron spin resonance studies of free radicals in irradiated single crystals of 5-methylcytosine. Int J Radiat PhysChem 3 117-129 Huttermann J, Ohlmann J, Schaefer A, Gatzweiler W (1991) The polymorphism of a cytosine anion studied by electron paramagnetic resonance spectroscopy. Int J Radiat Biol 59 1297-1311 Hwang CT, Stumpf CL, Yu Y-Q, Kentamaa HI (1999) Intrinsic acidity and redox properties of the adenine radical cation. Int J Mass Spectrom 182/183 253-259 Ide H, Otsuki N, Nishimoto S, Kagiya T (1985) Photoreduction of thymine glycol sensitized by aromatic amines in aqueous solution. J Chem Soc Perkin Trans 2 1387-1392 Idris Ali KM, Scholes G (1980) Analysis of radiolysis products of aqueous uracil + N20 solutions. J Chem Soc Faraday Trans 176 449-456... 

Fig. 8.3. An example of a gas chromatogram of the base-damage to DNA after exposure to hydroxyl radicals (generated radiolytically) - study of the trimethyl-silylated acidic hydrolysate of the modified DNA (modified from Dizdaroglu, 1988 with permission). Peaks I, phosphoric acid II, thymine III and Ilia, cytosine IV and IVa adenine V and Va guanine I uracil 2 5,6-dihydrothymine 3 5-hydroxy-5,6-dihydrothymine 4 5-hydroxyuracil 5 5-hydroxy-5,6-dihydrouracil 6 5-hydroxycytosine 7 cis-thymine glycol 8 /ra .s-thymine glycol 9 5,6-dihydroxyuracil 10 4,6-diamino-5-formamidopyr-imidine 11 8-hydroxyadenine 12 2,6-diamino-4-hydroxy-5-formamidopyrimidine 13...

Poly-9-(f -methacryloyloxyethyl)adenine (polyMAOA, 25 a), poly-l-(fi-methacryloyl-oxyethyl)uracil (polyMAOU, 27 a), -thymine (poly-MAOT, 29 a), poly-9-(f -acryloyl-oxyethyl)adenine (polyAOA, 25b), poly-1 -(fi-acryloyloxyethyl)uracil (polyAOU, 27b) and -thymine (polyAOT, 29 b) were prepared by free-radical polymerization of their corresponding monomers26,27). PolyMAOA and polyAOA are soluble in DMSO, ethylene glycol and acidic aqueous solution (below pH 3), while the polymers having uracil and thymine moieties are soluble in DMSO, DMF and alkaline aqueous solution (above pH 10). 

Figure 3. OH radical-induced degradation of thymine. Oxidation involves either OH addition to the C5-06 double bond or OH-mediated hydrogen abstraction from the methyl group. Molecular oxygen then adds to the resulting carbon-centered radicals. This reaction yields hydroperoxide that further evolves into stable products, such as thymidine glycol (ThdGly), 5-hydroxymethyl-uracil (HMdUrd) and 5 formyl-uracil (5-FordUrd). N- represents the bond to the DNA backbone.

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