2-(3,3-dimethyl-1-butyn-1-yl)adenosine | 1470001-54-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-(3,3-dimethyl-1-butyn-1-yl)adenosine
• CAS: 1470001-54-7
• 化学式: C₁₆H₂₁N₅O₄
• 分子量: 347.374
• InChiKey: BWOMDXNXWAIBOU-PMXXHBEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.58
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  139.54
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-(3,3-dimethyl-1-butyn-1-yl)adenosine 在 氨基磺酰氯 、 对甲苯磺酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 34.0h， 生成 2-(3,3-dimethyl-1-butyn-1-yl)-2′,3′-O-isopropylidene-5′-O-(sulfamoyl)adenosine
  参考文献：
  名称：

  Bisubstrate Inhibitors of Biotin Protein Ligase in Mycobacterium tuberculosis Resistant to Cyclonucleoside Formation

  摘要：

  Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is the leading cause of bacterial infectious disease mortality. Biotin protein ligase (BirA) globally regulates lipid metabolism in Mtb through the posttranslational biotinylation of acyl coenzyme A carboxylases (ACCs) involved in lipid biosynthesis and is essential for Mtb survival. We previously developed a rationally designed bisubstrate inhibitor of BirA that displays potent enzyme inhibition and whole cell activity against multidrug resistant and extensively drug resistant Mtb strains. Here we present the design, synthesis, and evaluation of a focused series of inhibitors, which are resistant to cyclonucleoside formation, a key decomposition pathway of our initial analogue. Improved chemical stability is realized through replacement of the adenosyl N-3 nitrogen and C-5' oxygen atom with carbon as well as incorporation of a bulky group on the nucleobase to prevent the required synconformation necessary for proper alignment of N-3 with C-5'.

  DOI：

  10.1021/ml400328a
• 作为产物：
  描述：

  3,3-二甲基-1-丁炔 、 2-碘腺苷 在 copper(l) iodide 、 bis(triphenylphosphine)palladium(II) dichloride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以77%的产率得到2-(3,3-dimethyl-1-butyn-1-yl)adenosine
  参考文献：
  名称：

  Bisubstrate Inhibitors of Biotin Protein Ligase in Mycobacterium tuberculosis Resistant to Cyclonucleoside Formation

  摘要：

  Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is the leading cause of bacterial infectious disease mortality. Biotin protein ligase (BirA) globally regulates lipid metabolism in Mtb through the posttranslational biotinylation of acyl coenzyme A carboxylases (ACCs) involved in lipid biosynthesis and is essential for Mtb survival. We previously developed a rationally designed bisubstrate inhibitor of BirA that displays potent enzyme inhibition and whole cell activity against multidrug resistant and extensively drug resistant Mtb strains. Here we present the design, synthesis, and evaluation of a focused series of inhibitors, which are resistant to cyclonucleoside formation, a key decomposition pathway of our initial analogue. Improved chemical stability is realized through replacement of the adenosyl N-3 nitrogen and C-5' oxygen atom with carbon as well as incorporation of a bulky group on the nucleobase to prevent the required synconformation necessary for proper alignment of N-3 with C-5'.

  DOI：

  10.1021/ml400328a