5'-O-(methylphosphonyl)-2'-deoxythymidine | 73264-62-7

• 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: 5'-O-(methylphosphonyl)-2'-deoxythymidine
• 英文别名: [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-methylphosphinic acid
• CAS: 73264-62-7
• 化学式: C₁₁H₁₇N₂O₇P
• 分子量: 320.239
• InChiKey: YINQPWLGWDPMJU-DJLDLDEBSA-N

物化性质

• 密度：
  1.497±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-O-(methylphosphonyl)-2'-deoxythymidine 在 N,N'-羰基二咪唑 、 三丁基焦磷酸铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以18%的产率得到5'-O-(α-methylphosphonyl)-β,γ-pyrophosphoryl-2'-deoxythymidine
  参考文献：
  名称：

  模板导向的DNA中蛋白质-磷酸盐接触的干扰足迹。

  摘要：

  [图：见正文]我们已经开发出一种干扰蛋白-DNA复合物中接触的磷酸盐的干扰足迹的方法。使用合成的三磷酸酯类似物（αMe-dTTP）进行模板指导的酶促聚合，生成的产物具有修饰的核苷酸间键，扰乱​​了蛋白质-磷酸盐的接触。我们发现，在非水条件下（MeO- / MeOH）处理甲基膦二酸酯取代的延伸产物会导致在每个T残基处形成一个裂解产物，但在标准的哌啶水溶液裂解方案下进行处理时会导致两个裂解产物。

  DOI：

  10.1021/ol006792j
• 作为产物：
  描述：

  3'-O-acetylthymidine 在 吡啶 、 氢氧化钾 、 N,N'-二环己基碳二亚胺 作用下， 反应 10.0h， 生成 5'-O-(methylphosphonyl)-2'-deoxythymidine
  参考文献：
  名称：

  5′-Phosphonates of Ribonucleosides and 2′-Deoxyribonucleosides: Synthesis and Antiviral Activity

  摘要：

  5'-Phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-O-acylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5'-Hydrogenphosphonothioates of thymidine and 3'-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3'-O-acetylthymidine or 3'-deoxythymidine, respectively, followed by addition of powedered sulfur. 5'-O-methylenephosphonates of thymidine and 2'-deoxyadenosine were prepared by intramolecular reaction of corresponding 3'-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several viruses, including HSV-2 and CMV, but showed no activity. A few compounds insignificantly inhibited HIV-1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized anti-HIV action of 3'-azido-3'-deoxythymidine (AZT) and it indirectly showed that even some nucleoside 5'-phosphonates could be partly hydrolyzed in cell culture to corresponding nucleosides.

  DOI：

  10.1080/07328319308018558

文献信息

• Oligonucleotides having chiral phosphorus linkages
  申请人：——

  公开号：US20010008936A1

  公开（公告）日：2001-07-19

  Sequence-specific oligonucleotides are provided having substantially pure chiral Sp phosphorothioate, chiral Rp phosphorothioate, chiral Sp alkylphosphonate, chiral Rp alkylphosphonate, chiral Sp phosphoamidate, chiral Rp phosphoamidate, chiral Sp phosphotriester, and chiral Rp phosphotriester linkages. The novel oligonucleotides are prepared via a stereospecific SN 2 nucleophilic attack of a phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate anion on the 3′ position of a xylonucleotide. The reaction proceeds via inversion at the 3′ position of the xylo reactant species, resulting in the incorporation of phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate linked ribofuranosyl sugar moieties into the oligonucleotide.

  本发明提供了具有高度纯的手性Sp磷酸硫酯、手性Rp磷酸硫酯、手性Sp烷基膦酸酯、手性Rp烷基膦酸酯、手性Sp磷酰胺酸酯、手性Rp磷酰胺酸酯、手性Sp磷酸三酯和手性Rp磷酸三酯键的序列特异性寡核苷酸。新型寡核苷酸通过对木糖核苷酸的3'位置进行立体特异性的SN2亲核攻击制备而成，反应通过在木糖反应物种的3'位置进行反转，从而将磷酸二酯、磷酸硫酯、磷酸胺酯、磷酸三酯或烷基膦酸酯连接的核糖核苷糖基团并入寡核苷酸中。
• Preparation of phosphorothioate oligomers
  申请人：McGill University

  公开号：US20040097722A9

  公开（公告）日：2004-05-20

  Methods and intermediates for the preparation of oligomers containing diastereomerically enriched phosphorothioate linkages are disclosed.

  本发明揭示了制备含有对映异构富集的磷酸硫酯键寡聚物的方法和中间体。
• XIGUTI, XIROTAKA
  作者：XIGUTI, XIROTAKA

  DOI：——

  日期：——
• AGRAWAL, SUDHIR;COODCHILD, JOHN, TETRAHEDRON LETT., 28,(1987) N 31, 3539-3542
  作者：AGRAWAL, SUDHIR、COODCHILD, JOHN

  DOI：——

  日期：——
• OLIGONUCLEOTIDES HAVING CHIRAL PHOSPHORUS LINKAGES
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP0655088B1

  公开（公告）日：2002-07-24