57609-73-1

Usage

InChI:InChI=1/C6H11NO4/c8-2-5-4(10)1-6(11-5)7-3-9/h3-6,8,10H,1-2H2,(H,7,9)/t4-,5+,6-/m0/s1

Upstream product

• 50-89-5 thymidine 
• 951-77-9 2'-Deoxycytidine 
• 96221-62-4 trans-(5R,6R)-6-hydroxy-5-(2,2,6,6-tetramethyl-4-oxo-1-piperidinyl-N-oxide)-5,6-dihydrothymidine 
• 96221-62-4 trans-(5S,6S)-6-hydroxy-5-(2,2,6,6-tetramethyl-4-oxo-1-piperidinyl-N-oxide)-5,6-dihydrothymidine 

Downstream Products

• 155645-76-4 2-deoxy-5-O-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl-N-formamide 
• 155645-77-5 2-deoxy-5-O-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl-N-formamide-3-O-<(2-chlorophenyl)-(2-cyanoethyl)-phosphate> 

Relevant academic research and scientific papers

The reactions of thymine and thymidine with ozone

The ozonolysis of thymine and thymidine has been investigated by a product study complemented by kinetic studies using spectrophotometry, conductometry and stopped-flow with optical and conductometric detection. Material balance has been obtained. Ozonolysis of thymine (k = 3.4 × 104 dm3 mol-1 s-1) leads to the formation of the acidic (pKa = 4) hydroperoxide 1-hydroperoxymethylene-3-(2-oxopropanoyl)urea 5 (～34%), neutral hydroperoxides (possibly mainly 1-hydroperoxyhydroxymethyl-3-(2-oxopropanoyl)urea 6, total ～41%) and H2O2 (25%, with corresponding formation of 1-formyl-5-hydroxy-5-methylhydantoin 11). The organic hydroperoxides decay (～1.1 × 10-3 s-1 at 20°C, 1.3 × 10-4 s-1 at 3°C) releasing formic acid (formation of 5-hydroperoxy-5-methylhydantoin 18) and also to some extent H2O2 (and 11). After 100 min, the formic acid yield is 75%. Upon treatment at high pH, it increases to 100%. Reduction of the organic hydroperoxides with bis(2-hydroxyethyl) sulfide (k = 50 dm3 mol-1 s-1) leads to 11 whose subsequent treatment with base yields 5-hydroxy-5-methylhydantoin 13 in 100% yield. It is suggested that the Criegee ozonide formed upon reaction with ozone at the C(5)-C(6) double bond opens heterolytically in two directions with subsequent opening of the C(5)-C(6) bond. In the preferred route (75%), the positive charge resides at C(6). Deprotonation at N(1) gives rise to 5, while its reaction with water yields 6. Loss of formic acid yields 5-hydroperoxy-5-methylhydantoin 18. Reduction of 5 and 6 with the sulfide yields 11. In the minor route (25%), the positive charge remains at C(5) followed by a reaction with water. The resulting α-hydroxy hydroperoxide rapidly loses H2O2 (formation of 11). In basic solution, singlet dioxygen is formed (8%). The concomitant product, 5,6-dihydroxy-5,6-dihydrothymine has been detected. In the ozonolysis of thymidine, the rapid formation of conductance (k = 0.55 s-1) is due to the release of acetic acid (18%). In this reaction a short-lived hydroperoxide is destroyed. As a consequence of this, 25 s after ozonolysis the total hydroperoxide yield is only ～78% (including 8% H2O2). The products corresponding to acetic acid are suggested to be CO2 and N-(2-deoxy-β-D-erythropentofuranosyl)formylurea 22. A number of organic hydroperoxides have been detected by HPLC by post-column derivatisation with iodide. An acidic hydroperoxide such as 5 in the case of thymine is not among the products. Upon sulfide reduction, the organic hydroperoxides yield mainly (43-50%) N1-(2-deoxy-β-D-erythropentofuranosyl)-5-hydroxy-5- methylhydantoin 23. The reasons for some striking differences in the ozonolyses of thymine and thymidine are discussed.

Hydroxyl-radical-induced decomposition of 2'-deoxycytidine in aerated aqueous solutions

The stable products resulting from γ-irradiation of 2'-deoxycytidine in aerated aqueous solutions have been purified to homogeneity and characterized by MS and NMR analyses. The main group of products, which are similar in structure to those that arise from the ·OH-mediated decomposition of thymidine, included four diastereomers of 5,6-dihydroxy-5,6-dihydro-2'- deoxyuridine (2-5), 5-hydroxy-2'-deoxycytidine (6), two diastereomers of N1- (2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxyhydantoin (7 and 8), and N1- (2-deoxy-β-D-erythro-pentofuranosyl)formamide (9). These products are likely formed by way of either intermediate 5(6)-hydroxy-6(5)-peroxyl radicals or the corresponding hydroperoxides. In labeling experiments, 18O2 was incorporated into products 2-9 with about 30% label at C5 and 60% at C6. Several other products were observed in the γ-irradiation of 2'- deoxycytidine in aerated aqueous solutions. They included four isomeric nucleosides of biuret (10-13), two diastereomers of N1-(2-deoxy-β-D- erythro-pentofuranosyl)-1-carbamoyl-2-oxo-4,5-dihydroxyimidazoline (14, 15), and aminocarbonyl[2-(2-deoxy-β-D-erythro-pentofuranosyl)amino]-2-oxo- ethylcarbamic acid (16). The first step in the formation of these products is probably intramolecular addition of the 5-hydroxy-6-hydroperoxide to C4 of the pyrimidine ring, resulting in a 4,6-endoperoxide which decomposes into an open-chain α-hydroxyaldehyde by C4-C5 cleavage. The formation of products 10-13 can be explained by subsequent fragmentation of the intermediate α- hydroxyaldehyde, whereas cyclization gives rise to products 14 and 15. In the case of products 16, a series of reactions have been proposed, starting with the rearrangement of the α-hydroxyaldehyde. The above pathways are supported by 18O2-labeling experiments. Finally, we characterized two diastereomers of 5',6-cyclo-5-hydroxy-5,6-dihydro-2'-deoxyuridine(17,81) in the γ- irradiation of 2'-deoxycytidine in aerated aqueous solutions. These products likely arise from initial ·OH abstraction of a proton from C(5') of the sugar moiety, followed by intramolecular addition of the resulting radical to C6 of the cytosine moiety. The ·OH-mediated decomposition of 2'- deoxycytidine in DNA is discussed.

Oxydation de la thymidine par l'ozone: comparaison avec l'action des radicaux hydroxyles

The reaction of the base moiety of the thymidine, one of the pyrimidinyl nucleosides, with ozone was examined.This reaction gives rise to five nucleosides which were isolated and characterised.The comparison with the current knowledge of the hydroxyl radical-mediated oxidations of thymidine, in aerated aqueous solution, shows that the ozone oxidation is specific.Indeed, the identified products obtained by the ozonolysis resulted from the opening of the C5-C6 bond.

Radiation-Induced Degradation of Purine and Pyrimidine 2'-Deoxyribonucleosides in Aqueous KBr Solutions

Steady-state γ-radiolysis of 5E-4 M pyrimidine and purine 2'-deoxyribonucleosides in aqueous solutions saturated with N2, N2O and O2, respectively, have been carried out in the presence of 0.1 M KBr.The main final degradation products have been isolated and characterised by various spectroscopic measurements including 1H and 13C NMR, UV, C.D. and mass spectrometry.The radiation-induced decomposition of thymidine is mostly accounted for by an ionic mechanism involving Br2, the decay product of Br2, as the reactive oxidising specie.On the other hand the degradation of the purine ring of 2'-deoxyadenosine and 2'-deoxyguanosine may be accounted for by the action of Br2 or Br3. - Keywords: 2'-Deoxyribonucleosides, Inorganic Radical, γ-Irradiation, Radical Reactions, Thymidine Oxidation

A 1H and 13C nmr study of the radiation-induced degradation products of 2'-deoxythymidine derivatives: N-(2'-deoxy-β-D-erythropentofuranosyl) formamide

N-(2'-Deoxy-β-D-eryhropentofuranosyl)formamide is an ionizing radiation induced degradation product of 2'-deoxythymidine.This work describes a facile chemical synthesis of this molecule, and discusses the results of an 1H and 13C nmr study.The rotational barrier to cis-trans isomerization about the amide linkage is calculated, and details of the molecular conformation of the cis and trans isomers in aqueous solution are presented.