6'-(R)-methyl-5-O-(5-azido-5,6-dideoxy-2,3-O-dibenzoyl-α-L-talofuranosyl)-3',4',6',6-tetra-O-acetyl-2′,1,3-triazidoparomamine | 1375073-89-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6'-(R)-methyl-5-O-(5-azido-5,6-dideoxy-2,3-O-dibenzoyl-α-L-talofuranosyl)-3',4',6',6-tetra-O-acetyl-2′,1,3-triazidoparomamine
• 英文别名: [(2R,3R,4R,5S)-5-[(1S,2S,3R,5S,6R)-2-acetyloxy-3,5-diazido-6-[(2S,3R,4R,5S,6R)-4,5-diacetyloxy-6-[(1R)-1-acetyloxyethyl]-3-azidooxan-2-yl]oxycyclohexyl]oxy-2-[(1S)-1-azidoethyl]-4-benzoyloxyoxolan-3-yl] benzoate
• CAS: 1375073-89-4
• 化学式: C₄₁H₄₆N₁₂O₁₆
• 分子量: 962.887
• InChiKey: NGSHEUMILYZVNM-RJTUCFLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  69
• 可旋转键数：
  24
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  252
• 氢给体数：
  0
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  6'-(R)-methyl-5-O-(5-azido-5,6-dideoxy-2,3-O-dibenzoyl-α-L-talofuranosyl)-3',4',6',6-tetra-O-acetyl-2′,1,3-triazidoparomamine 在 甲胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 9.17h， 生成 NB-124
  参考文献：
  名称：

  Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations

  摘要：

  Compelling evidence is now available that gentamicin and Geneticin (G418) can induce the mammalian ribosome to suppress disease-causing nonsense mutations and partially restore the expression of functional proteins. However, toxicity and relative lack of efficacy at subtoxic doses limit the use of gentamicin for suppression therapy. Although G418 exhibits the strongest activity, it is very cytotoxic even at low doses. We describe here the first systematic development of the novel aminoglycoside (S)-11 exhibiting similar in vitro and ex vivo activity to that of G418, while its cell toxicity is significantly lower than those of gentamicin and G418. Using a series of biochemical assays, we provide proof of principle that antibacterial activity and toxicity of aminoglycosides can be dissected from their suppression activity. The data further indicate that the increased specificity toward cytoplasmic ribosome correlates with the increased activity and that the decreased specificity toward mitochondrial ribosome confers the lowered cytotoxicity.

  DOI：

  10.1021/jm3012992
• 作为产物：
  描述：

  C₂₁H₂₉N₉O₁₁ 、 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以75%的产率得到6'-(R)-methyl-5-O-(5-azido-5,6-dideoxy-2,3-O-dibenzoyl-α-L-talofuranosyl)-3',4',6',6-tetra-O-acetyl-2′,1,3-triazidoparomamine
  参考文献：
  名称：

  Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations

  摘要：

  Compelling evidence is now available that gentamicin and Geneticin (G418) can induce the mammalian ribosome to suppress disease-causing nonsense mutations and partially restore the expression of functional proteins. However, toxicity and relative lack of efficacy at subtoxic doses limit the use of gentamicin for suppression therapy. Although G418 exhibits the strongest activity, it is very cytotoxic even at low doses. We describe here the first systematic development of the novel aminoglycoside (S)-11 exhibiting similar in vitro and ex vivo activity to that of G418, while its cell toxicity is significantly lower than those of gentamicin and G418. Using a series of biochemical assays, we provide proof of principle that antibacterial activity and toxicity of aminoglycosides can be dissected from their suppression activity. The data further indicate that the increased specificity toward cytoplasmic ribosome correlates with the increased activity and that the decreased specificity toward mitochondrial ribosome confers the lowered cytotoxicity.

  DOI：

  10.1021/jm3012992