1-(2-deoxy-β-D-erythro-pentafuranosyl)-5-hydroxy-5-methyl-hydantoin | 127707-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 1-(2-deoxy-β-D-erythro-pentafuranosyl)-5-hydroxy-5-methyl-hydantoin
• 英文别名: 5R* et 5S* N1-(desoxy-2-β-D-erythropentofurannosyl) hydroxy-5 methyl-5 hydantoine；N-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin；1-Deoxyribofuranosyl-5-hydroxy-5-methylhydantoin；N₁-(2-deoxy-β-D-erythropentofuranosyl)-5-hydroxy-5-methylhydantoin；N¹-(2-deoxy-β-D-ribofuranosyl)-5-hydroxy-5-methylhydantoin；1-(2-deoxy-β-D-ribofuranosyl)-5-hydroxy-5-methylhydantoin；Imidazolidine-deoxycytidine；5-hydroxy-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylimidazolidine-2,4-dione
• CAS: 127707-34-0
• 化学式: C₉H₁₄N₂O₆
• 分子量: 246.22
• InChiKey: FDZJCTAGSKTDIR-VCXZVJRYSA-N

物化性质

• 密度：
  1.607±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  beta-胸苷 在 臭氧 作用下， 以 水 为溶剂， 生成 1-(2-deoxy-β-D-erythro-pentafuranosyl)-5-hydroxy-5-methyl-hydantoin
  参考文献：
  名称：

  The reactions of thymine and thymidine with ozone

  摘要：

  胸腺嘧啶和胸腺嘧啶脱氧核苷的臭氧化反应已通过产物研究和利用分光光度法、电导法和带有光学和电导检测的停流技术的动力学研究得到补充。得到了物料平衡。胸腺嘧啶（k= 3.4 × 104 dm3 mol−1 s−1）的臭氧化反应导致形成酸性（pKa= 4）氢过氧化物1-羟过氧亚甲基-3-（2-氧丙酰基）脲5（约34%）、中性氢过氧化物（可能主要是1-羟过氧羟甲基-3-（2-氧丙酰基）脲6，总计约41%）和H2O2（25%，相应地形成1-甲酰基-5-羟基-5-甲基乙内酰脲11）。有机氢过氧化物衰减（20 °C下约为1.1 × 10−3 s−1，3 °C下为1.3 × 10−4 s−1），释放甲酸（形成5-羟过氧-5-甲基乙内酰脲18），也在一定程度上释放H2O2（和11）。100分钟后，甲酸产率为75%。在碱性高pH条件下处理后，产率增加到100%。用二（2-羟乙基）硫醚（k= 50 dm3 mol−1 s−1）还原有机氢过氧化物，产生11，其后续在碱性条件下的处理以100%的产率得到5-羟基-5-甲基乙内酰脲13。提出的机理是，在C(5)-C(6)双键与臭氧反应形成的Criegee臭氧化物在两个方向上异裂开环，随后C(5)-C(6)键断裂。在优先的路径（75%）中，正电荷位于C(6)。在N(1)处去质子化产生5，而其与水的反应产生6。失去甲酸形成5-羟过氧-5-甲基乙内酰脲18。用硫醚还原5和6产生11。在次要路径（25%）中，正电荷保持在C(5)，然后与水反应。产生的α-羟基氢过氧化物迅速失去H2O2（形成11）。在碱性溶液中，形成单线态双氧（8%）。同时产物5,6-二羟基-5,6-二氢胸腺嘧啶已被检测到。在胸腺嘧啶脱氧核苷的臭氧化反应中，快速形成的电导（k= 0.55 s−1）是由于释放乙酸（18%）。在这个反应中，一种短寿命的氢过氧化物被破坏。因此，臭氧化反应25秒后，总氢过氧化物产率仅为约78%（包括8% H2O2）。与乙酸对应的产物被认为是CO2和N-(2-脱氧-β-D-赤藓糖戊糖基)甲酰脲22。通过碘化物的柱后衍生化，通过HPLC检测到多种有机氢过氧化物。像胸腺嘧啶中的5这样的酸性氢过氧化物不在产物之列。用硫醚还原时，有机氢过氧化物主要（43-50%）产生的为N1-(2-脱氧-β-D-赤藓糖戊糖基)-5-羟基-5-甲基乙内酰脲23。讨论了胸腺嘧啶和胸腺嘧啶脱氧核苷臭氧化反应中一些显著差异的原因。

  DOI：

  10.1039/b204067k

文献信息

• Ozonolysis of Pyrimidine Nucleosides
  作者：Masaki Matsui、Tooru Inoue、Katsuyoshi Shibata、Hiroshige Muramatsu

  DOI：10.1246/bcsj.63.296

  日期：1990.1

  Cytidine, uridine, and thymidine are transformed into the ring-contracted 1-substituted derivatives by ozone. A plausible mechanism is proposed.

  胞苷、尿苷和胸苷通过臭氧转化为环收缩的1-取代衍生物。提出了一种合理的机制。
• Radiation-induced binding of 2,2,6,6-tetramethyl-1,4-piperidone-<i>N</i>-oxyl to thymidine in oxygen-free aqueous solutions. Isolation and characterization of the adducts
  作者：Maurice Berger、Jean Cadet、Jacques Ulrich

  DOI：10.1139/v85-002

  日期：1985.1.1

  Steady-state γ-radiolysis of deaerated aqueous solutions of thymidine has been carried out in the presence of 2,2,6,6-tetramethyl-1,4-piperidone-N-oxyl (TAN), a well-known radiosensitizing agent. The eight main radiation-induced TAN addition products to thymidine have been isolated and characterized by 1H and 13C nmr, cd, and fast-atom bombardment mass spectrometry measurements.

  已在 2,2,6,6-四甲基-1,4-哌啶酮-N-氧基 (TAN)（一种众所周知的放射增敏剂）存在下对脱气的胸苷水溶液进行稳态 γ-辐射分解。胸苷的八种主要辐射诱导的 TAN 加成产物已被分离出来，并通过 1H 和 13C nmr、cd 和快速原子轰击质谱测量进行表征。
• First characterisation of two important postulated intermediates in the formation of a HydT DNA lesion, a thymidine oxidation product
  作者：Emmanuel E. Psykarakis、Elli Chatzopoulou、Thanasis Gimisis

  DOI：10.1039/c8ob00378e

  日期：——

  number of environmental pollutants and endogenous oxidation agents form 1-(2-deoxy-β-D-ribofuranosyl)-5-hydroxy-5-methylhydantoin (HydT), an important DNA lesion resulting from thymidine oxidation. In this paper, two intermediates, postulated in the formation of HydT, have been characterised for the first time. The first, N1-formyl-N3-pyruvoylurea intermediate, was produced by the ozonolysis reaction of

  许多环境污染物和内源性氧化剂形成了1-（2-deoxy-β- D - rifurfuranosyl）-5-hydroxy-5-methylhydantoin（HydT），这是胸苷氧化导致的重要DNA损伤。在本文中，首次表征了HydT形成中假定的两种中间体。第一种N 1-甲酰基-N 3-丙酮酸中间体是通过2'，3'，5'- tri - O-乙酰基核糖-，3'，5'- di - O - TBS-和N 3，O 3′，O 5-三苄基保护的胸苷，经分解并取决于保护基和条件显示，单独或与受保护的-β - D-呋喃呋喃糖基-N 1-甲酰脲和甲酰胺产物一起生成HydT。另外，第二种且长期寻求的，开链的丙酮酸脲中间体是通过在保护的β- D-呋喃核糖基-，2-脱氧-β - D-呋喃核糖基-和2-deoxy-β- D-中从头合成而产生的。核吡喃糖基系统。已经确定了诱导HydT的乙内酰脲环环化的条件。从头开始使用的化学
• Thymidine Hydroperoxides: Structural Assignment, Conformational Features, and Thermal Decomposition in Water
  作者：J. R. Wagner、J. E. van Lier、M. Berger、J. Cadet

  DOI：10.1021/ja00085a001

  日期：1994.3

  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.
• Girault, I.; Molko, D.; Cadet, J., Journal de Chimie Physique et de Physico-Chimie Biologique, 1993, vol. 90, # 4, p. 863 - 870
  作者：Girault, I.、Molko, D.、Cadet, J.

  DOI：——

  日期：——