trans-(5R,6R)-5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine | 38709-49-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: trans-(5R,6R)-5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine
• 英文别名: (5R,6R)-5-hydroperoxy-6-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,3-diazinane-2,4-dione
• CAS: 38709-49-8
• 化学式: C₁₀H₁₆N₂O₈
• 分子量: 292.246
• InChiKey: QBYTYNBNJCXIBX-FZCTVIHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  149
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  trans-(5R,6R)-5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine 以 水 为溶剂， 生成 1-(2-deoxy-β-D-erythro-pentafuranosyl)-5-hydroxy-5-methyl-hydantoin 、 1-(2-Hydroperoxy-2-methyl-3-oxo-propionyl)-3-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-urea
  参考文献：
  名称：

  Thymidine Hydroperoxides: Structural Assignment, Conformational Features, and Thermal Decomposition in Water

  摘要：

  The primary products of DNA oxidation by free radicals are thymidine hydroperoxides, which include eight diastereomers of 5(6)-hydroxy-6(5)-hydroperoxy-5,6-dihydrothymidine and 5-(hydroperoxymethyl)-2'-deoxyuridine. The hydroperoxides were prepared by trifluoroperacetic acid oxidation of thymidine, which gave the four trans and cis diastereomers of 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine, and sensitized photooxidation of thymidine with 2-methyl-1,4-naphthoquinone and near-UV light, which gave the four trans and cis diasteromers of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine as well as 5-(hydroperoxymethyl)-2'-deoxyuridine. H-1 and C-13 NMR analyses suggested that the pyrimidine ring of thymidine 5,6-hydroxyhydroperoxides adopts four puckered conformations in which the orientations of the C6 hydroxy or hydroperoxy substituents are predominantly axial. The kinetics of decomposition of 5(6)-hydroxy-6(5)-hydroperoxy-5,6-dihydrothymidine were studied at 22, 37, and 55-degrees-C in ultrapure water. The cis diastereomers of each group were generally found to be more stable than the corresponding trans diastereomers. The enthalpy (DELTAH(double dagger)) and entropy (DELTAS(double dagger)) of decomposition were in the range of 22.9-25.2 kcal mol-1 (DELTAH(double dagger) and -7.4-+3.7 cal mol-1 deg-1 (DELTAS)(double dagger)) for 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine and in the range 28.5-35.2 kcal mol-1 (DELTAH(double dagger)) and +9.7-+30 cal mol-1 deg-1 (DELTAS(double dagger)) for 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine. The mechanism of decomposition was studied by analysis of stable and intermediate products: the major decomposition products of the trans and cis diasteromers of 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine were N-(2-deoxy-beta-D-erythro-pento-furanosyl)-5-hydroxy-5-methylbarbituric acid and N1-(2-deoxy-beta-D-erythro-pentofuranosyl-N3-tartronoylurea in neutral aqueous solutions; in contrast, the trans and cis diastereomers of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine were observed to undergo isomerization and ultimately decomposed into the 5R* and 5S* diastereomers of N-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin. On the basis of the above results, the mechanism of decomposition was proposed to involve either dehydration for 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine or ring-chain tautomerism followed by alpha-cleavage of an intermediate hydroperoxy aldehyde and subsequent ring closure for 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine.

  DOI：

  10.1021/ja00085a001
• 作为产物：
  描述：

  beta-胸苷 在 甲萘醌 、 氧气 作用下， 以 水 为溶剂， 反应 4.0h， 以1%的产率得到trans-(5R,6R)-5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine
  参考文献：
  名称：

  Thymidine Hydroperoxides: Structural Assignment, Conformational Features, and Thermal Decomposition in Water

  摘要：

  The primary products of DNA oxidation by free radicals are thymidine hydroperoxides, which include eight diastereomers of 5(6)-hydroxy-6(5)-hydroperoxy-5,6-dihydrothymidine and 5-(hydroperoxymethyl)-2'-deoxyuridine. The hydroperoxides were prepared by trifluoroperacetic acid oxidation of thymidine, which gave the four trans and cis diastereomers of 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine, and sensitized photooxidation of thymidine with 2-methyl-1,4-naphthoquinone and near-UV light, which gave the four trans and cis diasteromers of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine as well as 5-(hydroperoxymethyl)-2'-deoxyuridine. H-1 and C-13 NMR analyses suggested that the pyrimidine ring of thymidine 5,6-hydroxyhydroperoxides adopts four puckered conformations in which the orientations of the C6 hydroxy or hydroperoxy substituents are predominantly axial. The kinetics of decomposition of 5(6)-hydroxy-6(5)-hydroperoxy-5,6-dihydrothymidine were studied at 22, 37, and 55-degrees-C in ultrapure water. The cis diastereomers of each group were generally found to be more stable than the corresponding trans diastereomers. The enthalpy (DELTAH(double dagger)) and entropy (DELTAS(double dagger)) of decomposition were in the range of 22.9-25.2 kcal mol-1 (DELTAH(double dagger) and -7.4-+3.7 cal mol-1 deg-1 (DELTAS)(double dagger)) for 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine and in the range 28.5-35.2 kcal mol-1 (DELTAH(double dagger)) and +9.7-+30 cal mol-1 deg-1 (DELTAS(double dagger)) for 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine. The mechanism of decomposition was studied by analysis of stable and intermediate products: the major decomposition products of the trans and cis diasteromers of 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine were N-(2-deoxy-beta-D-erythro-pento-furanosyl)-5-hydroxy-5-methylbarbituric acid and N1-(2-deoxy-beta-D-erythro-pentofuranosyl-N3-tartronoylurea in neutral aqueous solutions; in contrast, the trans and cis diastereomers of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine were observed to undergo isomerization and ultimately decomposed into the 5R* and 5S* diastereomers of N-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin. On the basis of the above results, the mechanism of decomposition was proposed to involve either dehydration for 5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine or ring-chain tautomerism followed by alpha-cleavage of an intermediate hydroperoxy aldehyde and subsequent ring closure for 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine.

  DOI：

  10.1021/ja00085a001