N-D-biotinoyl-C-(2',3'-O-isopropylidene-5'-adenosyl)methansulfonamide triethylammonium

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: N-D-biotinoyl-C-(2',3'-O-isopropylidene-5'-adenosyl)methansulfonamide triethylammonium
• 化学式: C₆H₁₅N*C₂₁H₃₀N₈O₇S₂
• 分子量: 671.842
• InChiKey: HQFPQOGTFDUEOM-RGABNAQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.06
• 重原子数：
  45.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  226.92
• 氢给体数：
  6.0
• 氢受体数：
  14.0

反应信息

• 作为产物：
  描述：

  N,N-二[叔丁氧羰基]-2',3'-O-(异丙亚基)腺苷 在 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 戴斯-马丁氧化剂 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 58.75h， 生成 N-D-biotinoyl-C-(2',3'-O-isopropylidene-5'-adenosyl)methansulfonamide triethylammonium
  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

文献信息

• Bisubstrate Inhibitors of Biotin Protein Ligase in <i>Mycobacterium tuberculosis</i> Resistant to Cyclonucleoside Formation
  作者：Ce Shi、Divya Tiwari、Daniel J. Wilson、Christopher L. Seiler、Dirk Schnappinger、Courtney C. Aldrich

  DOI：10.1021/ml400328a

  日期：2013.12.12

  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'.