3'-azido-3'-deoxythymidin-5'-yl bis<(pivaloyloxy)methyl> phosphate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: 3'-azido-3'-deoxythymidin-5'-yl bis<(pivaloyloxy)methyl> phosphate
• 英文别名: 3'-azido-3'-deoxythymidin-5'-yl bis[(pivaloyloxy)methyl] phosphate；[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate；[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
• 化学式: C₂₂H₃₄N₅O₁₁P
• 分子量: 575.513
• InChiKey: FALKBFDMDYWFSF-ARFHVFGLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  170
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  ((hydroxyphosphoryl)bis(oxy))bis(methylene) bis(2,2-dimethylpropanoate) 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 3'-azido-3'-deoxythymidin-5'-yl bis<(pivaloyloxy)methyl> phosphate
  参考文献：
  名称：

  Efficient Synthesis of Phosphorylated Prodrugs with Bis(POM)-phosphoryl Chloride

  摘要：

  An efficient method for the synthesis of phosphorylated prodrugs is described. The preparation of various bis-pivaloyloxymethyl (POM) phosphate triesters was accomplished in moderate to good yields with the use of bis(POM) phosphoryl chloride under mild conditions.

  DOI：

  10.1021/ol049714v

文献信息

• Mononucleoside Phosphotriester Derivatives with S-Acyl-2-thioethyl Bioreversible Phosphate-Protecting Groups: Intracellular Delivery of 3'-Azido-2',3'-dideoxythymidine 5'-Monophosphate
  作者：Isabelle Lefebvre、Christian Perigaud、Alain Pompon、Anne-Marie Aubertin、Jean-Luc Girardet、Andre Kirn、Gilles Gosselin、Jean-Louis Imbach

  DOI：10.1021/jm00020a007

  日期：1995.9

  The synthesis, in vitro anti-HIV-1 activity, and decomposition pathways of several mononucleoside phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) incorporating a new kind of carboxylate esterase-labile transient phosphate-protecting group, namely, S-acyl-2-thioethyl, are reported. All the described compounds showed marked antiviral activity in thymidine kinase-deficient CEM cells

  3'-叠氮基2'，3'-二脱氧胸苷（AZT）的几种单核苷磷酸三酯衍生物的合成，体外抗HIV-1活性和分解途径，结合了一种新型的羧酸酯酶不稳定的瞬时磷酸保护基团据报道，即S-酰基-2-硫代乙基。所有描述的化合物在胸腺嘧啶激酶缺失的CEM细胞中均表现出显着的抗病毒活性，其中AZT实际上是无活性的。结果强烈支持这样的假说，即这种前核苷酸通过AZT的5'-单核苷酸的细胞内递送发挥其生物学作用。在细胞提取物和培养基中的分解研究证实了这一点。
• Efficient Synthesis of Phosphorylated Prodrugs with Bis(POM)-phosphoryl Chloride
  作者：Yousang Hwang、Philip A. Cole

  DOI：10.1021/ol049714v

  日期：2004.5.1

  An efficient method for the synthesis of phosphorylated prodrugs is described. The preparation of various bis-pivaloyloxymethyl (POM) phosphate triesters was accomplished in moderate to good yields with the use of bis(POM) phosphoryl chloride under mild conditions.