3,5'-cyclo-2'-deoxyxanthosine | 1070789-83-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 3,5'-cyclo-2'-deoxyxanthosine
• 英文别名: (10R,11S,13R)-11-hydroxy-15-oxa-1,3,6,8-tetrazatetracyclo[6.5.1.110,13.04,14]pentadeca-2,4(14)-diene-5,7-dione
• CAS: 1070789-83-1
• 化学式: C₁₀H₁₀N₄O₄
• 分子量: 250.214
• InChiKey: VHFZILUISSTDHW-KVQBGUIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  96.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5'-cyclo-2'-deoxyxanthosine 在 盐酸 、 水 作用下， 反应 1.0h， 生成 3-[[(2R,3S)-3,5-dihydroxyoxolan-2-yl]methyl]-7H-purine-2,6-dione
  参考文献：
  名称：

  α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT

  摘要：

  We report synthesis and characterization of a complete set of alpha,beta-methylene-2'-dNTPs (alpha,beta-m-dNTP; N = A, C, T, G, 12-15) in which the alpha,beta-oxygen linkage of natural dNTP was replaced by a methylene group. These nucleotides were designed to be noncleavable substrates for DNA polymerases. Synthesis entails preparation of 2'-deoxynucleoside 5'-diphosphate precursors, followed by an enzymatic gamma-phosphorylation. All four synthesized alpha,beta-m-dNTPs were found to be potent inhibitors of polymerase beta, with K-i values ranging 1-5 mu M. During preparation of the dG and dT derivatives of alpha,beta-methylene diphosphate, we also isolated significant amounts of 3,5'-cyclo-dG (16) and 2,5'-cyclo-dT (17), respectively. These novel 2'-deoxycyclonucleosides were formed via a base-catalyzed intramolecular cyclization (N3 -> C5' and O2 -> C5' respectively). In acidic solution, both 16 and 17 underwent glycolysis, followed by complete depurination. When exposed to alkaline conditions, 16 underwent an oxidative deamination to produce 3,5'-cyc1o-2'-deoxyxanthosine (19), whereas 17 was hydrolyzed exclusively to dT.

  DOI：

  10.1021/jm800692a
• 作为产物：
  描述：

  2,5'-环-2'-脱氧胸苷 在 sodium hydroxide 、 水 作用下， 反应 41.0h， 生成 3,5'-cyclo-2'-deoxyxanthosine
  参考文献：
  名称：

  α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT

  摘要：

  We report synthesis and characterization of a complete set of alpha,beta-methylene-2'-dNTPs (alpha,beta-m-dNTP; N = A, C, T, G, 12-15) in which the alpha,beta-oxygen linkage of natural dNTP was replaced by a methylene group. These nucleotides were designed to be noncleavable substrates for DNA polymerases. Synthesis entails preparation of 2'-deoxynucleoside 5'-diphosphate precursors, followed by an enzymatic gamma-phosphorylation. All four synthesized alpha,beta-m-dNTPs were found to be potent inhibitors of polymerase beta, with K-i values ranging 1-5 mu M. During preparation of the dG and dT derivatives of alpha,beta-methylene diphosphate, we also isolated significant amounts of 3,5'-cyclo-dG (16) and 2,5'-cyclo-dT (17), respectively. These novel 2'-deoxycyclonucleosides were formed via a base-catalyzed intramolecular cyclization (N3 -> C5' and O2 -> C5' respectively). In acidic solution, both 16 and 17 underwent glycolysis, followed by complete depurination. When exposed to alkaline conditions, 16 underwent an oxidative deamination to produce 3,5'-cyc1o-2'-deoxyxanthosine (19), whereas 17 was hydrolyzed exclusively to dT.

  DOI：

  10.1021/jm800692a

文献信息

• α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT
  作者：Fengting Liang、Nidhi Jain、Troy Hutchens、David D. Shock、William A. Beard、Samuel H. Wilson、M. Paul Chiarelli、Bongsup P. Cho

  DOI：10.1021/jm800692a

  日期：2008.10.23

  We report synthesis and characterization of a complete set of alpha,beta-methylene-2'-dNTPs (alpha,beta-m-dNTP; N = A, C, T, G, 12-15) in which the alpha,beta-oxygen linkage of natural dNTP was replaced by a methylene group. These nucleotides were designed to be noncleavable substrates for DNA polymerases. Synthesis entails preparation of 2'-deoxynucleoside 5'-diphosphate precursors, followed by an enzymatic gamma-phosphorylation. All four synthesized alpha,beta-m-dNTPs were found to be potent inhibitors of polymerase beta, with K-i values ranging 1-5 mu M. During preparation of the dG and dT derivatives of alpha,beta-methylene diphosphate, we also isolated significant amounts of 3,5'-cyclo-dG (16) and 2,5'-cyclo-dT (17), respectively. These novel 2'-deoxycyclonucleosides were formed via a base-catalyzed intramolecular cyclization (N3 -> C5' and O2 -> C5' respectively). In acidic solution, both 16 and 17 underwent glycolysis, followed by complete depurination. When exposed to alkaline conditions, 16 underwent an oxidative deamination to produce 3,5'-cyc1o-2'-deoxyxanthosine (19), whereas 17 was hydrolyzed exclusively to dT.