| 875105-30-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 875105-30-9
• 化学式: C₈₀H₉₂N₆O₂₇S
• 分子量: 1601.7
• InChiKey: RHFANXBJUUICLK-OEQMROKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  114.0
• 可旋转键数：
  32.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  450.11
• 氢给体数：
  12.0
• 氢受体数：
  27.0

反应信息

• 作为反应物：
  描述：

  在 palladium on activated charcoal 氢气 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.32 kPa 条件下， 反应 48.0h， 以60%的产率得到
  参考文献：
  名称：

  Exploring the Use of Conformationally Locked Aminoglycosides as a New Strategy to Overcome Bacterial Resistance

  摘要：

  The emergence of bacterial resistance to the major classes of antibiotics has become a serious problem over recent years. For aminoglycosides, the major biochemical mechanism for bacterial resistance is the enzymatic modification of the drug. Interestingly, in several cases, the oligosaccharide conformation recognized by the ribosomic RNA and the enzymes responsible for the antibiotic inactivation is remarkably different. This observation suggests a possible structure-based chemical strategy to overcome bacterial resistance; in principle, it should be possible to design a conformationally locked oligosaccharide that still retains antibiotic activity but that is not susceptible to enzymatic inactivation. To explore the scope and limitations of this strategy, we have synthesized several aminoglycoside derivatives locked in the ribosome-bound "bioactive" conformation. The effect of the structural preorganization on RNA binding, together with its influence on the aminoglycoside inactivation by several enzymes involved in bacterial resistance, has been studied. Our results indicate that the conformational constraint has a modest effect on their interaction with ribosomal RNA. In contrast, it may display a large impact on their enzymatic inactivation. Thus, the work presented herein provides a key example of how the conformational differences exhibited by these ligands within the binding pockets of the ribosome and of those enzymes involved in bacterial resistance can, in favorable cases, be exploited for designing new antibiotic derivatives with improved activity in resistant strains.

  DOI：

  10.1021/ja0543144
• 作为产物：
  描述：

  在 甲醇 、 potassium cyanide 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 以58%的产率得到
  参考文献：
  名称：

  Exploring the Use of Conformationally Locked Aminoglycosides as a New Strategy to Overcome Bacterial Resistance

  摘要：

  The emergence of bacterial resistance to the major classes of antibiotics has become a serious problem over recent years. For aminoglycosides, the major biochemical mechanism for bacterial resistance is the enzymatic modification of the drug. Interestingly, in several cases, the oligosaccharide conformation recognized by the ribosomic RNA and the enzymes responsible for the antibiotic inactivation is remarkably different. This observation suggests a possible structure-based chemical strategy to overcome bacterial resistance; in principle, it should be possible to design a conformationally locked oligosaccharide that still retains antibiotic activity but that is not susceptible to enzymatic inactivation. To explore the scope and limitations of this strategy, we have synthesized several aminoglycoside derivatives locked in the ribosome-bound "bioactive" conformation. The effect of the structural preorganization on RNA binding, together with its influence on the aminoglycoside inactivation by several enzymes involved in bacterial resistance, has been studied. Our results indicate that the conformational constraint has a modest effect on their interaction with ribosomal RNA. In contrast, it may display a large impact on their enzymatic inactivation. Thus, the work presented herein provides a key example of how the conformational differences exhibited by these ligands within the binding pockets of the ribosome and of those enzymes involved in bacterial resistance can, in favorable cases, be exploited for designing new antibiotic derivatives with improved activity in resistant strains.

  DOI：

  10.1021/ja0543144