2-(((2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(((2-sulfido-1,3,2-dioxaphospholan-2-yl)oxy)methyl)tetrahydrofuran-3-yl)oxy)-1,3,2-dioxaphospholane 2-sulfide | 1521248-96-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 2-(((2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(((2-sulfido-1,3,2-dioxaphospholan-2-yl)oxy)methyl)tetrahydrofuran-3-yl)oxy)-1,3,2-dioxaphospholane 2-sulfide
• CAS: 1521248-96-3
• 化学式: C₁₄H₁₉N₅O₇P₂S₂
• 分子量: 495.414
• InChiKey: AXFOXRHQAIXQNI-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.64
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  134.23
• 氢给体数：
  1.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  2-(((2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(((2-sulfido-1,3,2-dioxaphospholan-2-yl)oxy)methyl)tetrahydrofuran-3-yl)oxy)-1,3,2-dioxaphospholane 2-sulfide 在 sodium cyanide 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Nucleoside—2′,3′/3′,5′-Bis(thio)phosphate Analogues Are Promising Antioxidants Acting Mainly via Cu⁺/Fe²⁺ Ion Chelation

  摘要：

  We synthesized a series of adenine/guanine 2',3'- or 3',5'-bisphosphate and -bisphosphorothioate analogues, 1-6, as potential Cu+/Fe2+ chelators, with a view to apply them as biocompatible and water-soluble antioxidants. We found that electron paramagnetic resonance (EPR)-monitored inhibition of OH radicals production from H2O2, in an Fe2+-H2O2 system, by bisphosphate derivatives 1, 3, and 5 (IC50 = 36, 24, and 40 mu M, respectively), was more effective than it was by ethylenediaminetetraacetic acid (EDTA), by a factor of 1.5, 2, and 1.4, respectively. Moreover, 2'-deoxyadenosine-3',5'-bisphosphate, 1, was 1.8- and 4.7-times more potent than adenosine 5'-monophosphate (AMP) and adenosine S'-diphosphate (ADP), respectively. The bisphosphorothioate derivatives 2, 4, and 6 (IC50 = 92, 50, and 80 mu M, respectively), exhibited a dual antioxidant activity, acting as both metal-ion chelators and radical scavengers [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay data indicates IC50 = 50, 70, and 108 mu M vs 27 mu M for Trolox]. Only 2'-deoxyadenosine-3',5'-bisphosphorothioate, 2, exhibited good inhibition of Cu+-induced H2O2 decomposition (IC50 = 78 vs 224 mu M for EDTA). Nucleoside-bisphosphorothioate analogues (2, 4, and 6) were weaker inhibitors than the corresponding bisphosphate analogues (1, 3, and 5), due to intramolecular oxidation under Fenton reaction conditions. H-1- and P-31 NMR monitored Cu+ titration of 2, showed that Cu+ was coordinated by both 3',5'-bisphosphorothioate groups, as well as N7-nitrogen atom, while adenosine-2',3'-bisphosphorothioate, 6, coordinated Cu+ only by 2',3'-bisphosphorothioate groups. In conclusion, an additional terminal phosphate group on AMP/guanosine S'-monophosphate (GMP) resulted in Fe2+-selective chelators highly potent as Fenton reaction inhibitors.

  DOI：

  10.1021/ic402671q
• 作为产物：
  描述：

  2'-脱氧腺苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 3.0h， 生成 2-(((2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-(((2-sulfido-1,3,2-dioxaphospholan-2-yl)oxy)methyl)tetrahydrofuran-3-yl)oxy)-1,3,2-dioxaphospholane 2-sulfide
  参考文献：
  名称：

  Nucleoside—2′,3′/3′,5′-Bis(thio)phosphate Analogues Are Promising Antioxidants Acting Mainly via Cu⁺/Fe²⁺ Ion Chelation

  摘要：

  We synthesized a series of adenine/guanine 2',3'- or 3',5'-bisphosphate and -bisphosphorothioate analogues, 1-6, as potential Cu+/Fe2+ chelators, with a view to apply them as biocompatible and water-soluble antioxidants. We found that electron paramagnetic resonance (EPR)-monitored inhibition of OH radicals production from H2O2, in an Fe2+-H2O2 system, by bisphosphate derivatives 1, 3, and 5 (IC50 = 36, 24, and 40 mu M, respectively), was more effective than it was by ethylenediaminetetraacetic acid (EDTA), by a factor of 1.5, 2, and 1.4, respectively. Moreover, 2'-deoxyadenosine-3',5'-bisphosphate, 1, was 1.8- and 4.7-times more potent than adenosine 5'-monophosphate (AMP) and adenosine S'-diphosphate (ADP), respectively. The bisphosphorothioate derivatives 2, 4, and 6 (IC50 = 92, 50, and 80 mu M, respectively), exhibited a dual antioxidant activity, acting as both metal-ion chelators and radical scavengers [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay data indicates IC50 = 50, 70, and 108 mu M vs 27 mu M for Trolox]. Only 2'-deoxyadenosine-3',5'-bisphosphorothioate, 2, exhibited good inhibition of Cu+-induced H2O2 decomposition (IC50 = 78 vs 224 mu M for EDTA). Nucleoside-bisphosphorothioate analogues (2, 4, and 6) were weaker inhibitors than the corresponding bisphosphate analogues (1, 3, and 5), due to intramolecular oxidation under Fenton reaction conditions. H-1- and P-31 NMR monitored Cu+ titration of 2, showed that Cu+ was coordinated by both 3',5'-bisphosphorothioate groups, as well as N7-nitrogen atom, while adenosine-2',3'-bisphosphorothioate, 6, coordinated Cu+ only by 2',3'-bisphosphorothioate groups. In conclusion, an additional terminal phosphate group on AMP/guanosine S'-monophosphate (GMP) resulted in Fe2+-selective chelators highly potent as Fenton reaction inhibitors.

  DOI：

  10.1021/ic402671q