(5S,6S)-cis-5-hydroxy-6-phenylthio-5,6-dihydrothymidine | 793684-15-8

• 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: (5S,6S)-cis-5-hydroxy-6-phenylthio-5,6-dihydrothymidine
• 英文别名: 5R,6S-5,6-dihydro-5-hydroxy-6-thiophenyl-thymidine
• CAS: 793684-15-8
• 化学式: C₁₆H₂₀N₂O₆S
• 分子量: 368.411
• InChiKey: BZSFJWGTPDFVAX-LYKUNHBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.12
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119.33
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (5S,6S)-cis-5-hydroxy-6-phenylthio-5,6-dihydrothymidine 在 4,5-二氰基咪唑 、 氨 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.67h， 生成
  参考文献：
  名称：

  Independent Generation of the 5-Hydroxy-5,6-dihydrothymidin-6-yl Radical and Its Reactivity in Dinucleoside Monophosphates

  摘要：

  Hydroxyl radical is a major reactive oxygen species produced by gamma-radiolysis of water or Fenton reaction. It attacks pyrimidine bases and gives the 5-hydroxy-5,6-dihydropyrimidin-6-yl radical as the major product. Here we report the synthesis of all four stereoisomers of 5-hydroxy-6-phenylthio-5,6-dihydrothymidine (T*), which, upon 254 nm UV irradiation, give rise to the 5-hydroxy-5,6-dihydrothymidin-6-yl radical (1). We also incorporated the photolabile radical precursors into dinucleoside monophosphates d(GT*) and d(TT*) and characterized major products resulting from the 254-nm irradiation of these dinucleoside monophosphates. Our results showed that, under anaerobic conditions, the most abundant product emanating from the 254-nm irradiation of d(GT*) and d(TT*) is an abasic site lesion. Products with the thymine portion being modified to thymine glycol and 5-hydroxy-5,6-dihydrothymine were also observed. In addition, we demonstrated that radical I can attack the C8 carbon atom of its 5' neighboring guanine and give rise to a novel cross-link lesion. Moreover, LC-MS/MS results showed that gamma-radiation of d(GT) under anaerobic condition yielded the same type of cross-link lesions.

  DOI：

  10.1021/ja048492t
• 作为产物：
  描述：

  O,O-(5S,6S)-trans-(-)-5-bromo-6-hydroxy-5,6-dihydrothymidine-3',5'-diyldiacetate 在 吡啶 、 氨 、 zinc(II) oxide 作用下， 以 甲醇 、 苯 为溶剂， 生成 (5S,6S)-cis-5-hydroxy-6-phenylthio-5,6-dihydrothymidine
  参考文献：
  名称：

  Independent Generation of the 5-Hydroxy-5,6-dihydrothymidin-6-yl Radical and Its Reactivity in Dinucleoside Monophosphates

  摘要：

  Hydroxyl radical is a major reactive oxygen species produced by gamma-radiolysis of water or Fenton reaction. It attacks pyrimidine bases and gives the 5-hydroxy-5,6-dihydropyrimidin-6-yl radical as the major product. Here we report the synthesis of all four stereoisomers of 5-hydroxy-6-phenylthio-5,6-dihydrothymidine (T*), which, upon 254 nm UV irradiation, give rise to the 5-hydroxy-5,6-dihydrothymidin-6-yl radical (1). We also incorporated the photolabile radical precursors into dinucleoside monophosphates d(GT*) and d(TT*) and characterized major products resulting from the 254-nm irradiation of these dinucleoside monophosphates. Our results showed that, under anaerobic conditions, the most abundant product emanating from the 254-nm irradiation of d(GT*) and d(TT*) is an abasic site lesion. Products with the thymine portion being modified to thymine glycol and 5-hydroxy-5,6-dihydrothymine were also observed. In addition, we demonstrated that radical I can attack the C8 carbon atom of its 5' neighboring guanine and give rise to a novel cross-link lesion. Moreover, LC-MS/MS results showed that gamma-radiation of d(GT) under anaerobic condition yielded the same type of cross-link lesions.

  DOI：

  10.1021/ja048492t

文献信息

• Photochemical Generation and Reactivity of the Major Hydroxyl Radical Adduct of Thymidine
  作者：Joanna Maria N. San Pedro、Marc M. Greenberg

  DOI：10.1021/ol301109z

  日期：2012.6.1

  resulting from hydroxyl radical addition to C5 of the pyrimidine, is produced via 350 nm photolysis of a 2,5-dimethoxyphenylsulfide precursor (2). Competition between O2 and thiol for 1 suggests that the radical reacts relatively slowly with β-mercaptoethanol compared to other alkyl radicals. Overall, aryl sulfide 2 should be an effective precursor for the major hydroxyl radical adduct of thymidine in

  5,6-二氢-5-羟基胸苷-6-基自由基 ( 1 ) 是由羟基自由基加成到嘧啶的 C5 产生的主要反应中间体，通过 2,5-二甲氧基苯硫醚前体 ( 2 ) 的350 nm 光解产生. O 2和硫醇之间的1竞争表明，与其他烷基自由基相比，该自由基与 β-巯基乙醇的反应相对较慢。总的来说，芳基硫化物2应该是 DNA 中胸苷主要羟基自由基加合物的有效前体。