1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylbarbituric acid | 38241-09-7

• 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: 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylbarbituric acid
• 英文别名: N-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylbarbituric acid；1-(β-D-erythro-2-deoxy-pentofuranosyl)-5-hydroxy-5-methyl-pyrimidine-2,4,6-trione；Desoxy-2-β-D-ribofuranosyl-1-hydroxy-5-methyl-5-barbitursaeure
• CAS: 38241-09-7
• 化学式: C₁₀H₁₄N₂O₇
• 分子量: 274.23
• InChiKey: HZOYGGAJRAGAGV-JKGXRCIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.72
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  136.4
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  trans(5R,6R)-5-hydroxy-6-hydroperoxy-5,6-dihydrothymidine 以 水 为溶剂， 生成 N1-(2-deoxy-β-D-erythro-pentofuranosyl)-N3-tartronoylurea 、 1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylbarbituric acid
  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

文献信息

• Sonochemical transformation of thymidine: A mass spectrometric study
  作者：Jisha Chandran、Usha K. Aravind、C.T. Aravindakumar

  DOI：10.1016/j.ultsonch.2015.05.016

  日期：2015.11

  Ultrasound is extensively used in medical field for a number of applications including targeted killing of cancer cells. DNA is one of the most susceptible entities in any kind of free radical induced reactions in living systems. In the present work, the transformation of thymidine (dT) induced by ultrasound (US) was investigated using high resolution mass spectrometry (LC-Q-ToF-MS). dT was subjected

  超声在医学领域已广泛用于许多应用，包括靶向杀死癌细胞。DNA是生命系统中任何种类的自由基诱导的反应中最易感的实体之一。在当前的工作中，使用高分辨率质谱（LC-Q-ToF-MS）研究了超声（US）诱导的胸腺嘧啶核苷（dT）的转化。在充气和氩气饱和条件下，dT在四种不同的频率（200、350、620和1000 kHz）和三种功率密度（10.5、24.5和42 W / mL）下进行声处理。通过LC-Q-ToF-MS检测到总共20种修饰的核苷，包括未完全表征的dT二聚化合物。在这些产物中，仅在氩气气氛中获得了七种，而仅在充气条件下获得了两种。在确定的产品中，有基础改性产品和糖改性产品。产物是通过羟基自由基和氢原子的反应形成的。在充气条件下，反应通过氢过氧化物的形成而进行，而在氩气气氛中歧化和自由基重组占主导。该研究提供了dT的声化学转化途径的完整图片，该途径与超声暴露下的DNA损伤有关。