acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl pyrrolidine-1-carbodithioate | 1273127-96-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl pyrrolidine-1-carbodithioate
• CAS: 1273127-96-0
• 化学式: C₁₉H₂₈N₂O₈S₂
• 分子量: 476.572
• InChiKey: OVDGVZOIXGYHQB-ZKXLYKBJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.76
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  120.47
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl pyrrolidine-1-carbodithioate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以78%的产率得到2-acetamido-2-deoxy-β-D-glucopyranosyl pyrrolidine-1-carbodithioate
  参考文献：
  名称：

  Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives

  摘要：

  The present study was undertaken to optimize the anti-tubercular activity of 2-acetamido-2-deoxy-beta-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313, Glc-NAc-DMDC), a lead compound previously reported by us. Structural modifications of OCT313 included the replacements of the DMDC group at C-1 by pyrrolidine dithiocarbamate (PDTC) and the acetyl group at C-2 by either propyl, butyl, benzyl or oleic acid groups. The antimycobacterial activities of these derivatives were evaluated against Mycobacterium tuberculosis (MTB). Glc-NAc-pyrrolidine dithiocarbamate (OCT313HK, Glc-NAc-PDTC) exhibited the most potent anti-tubercular activity with the minimal inhibitory concentration (MIC) of 6.25-12.5 mu g/ml. The antibacterial activity of OCT313HK was highly specific to MTB and Mycobacterium bovis BCG, but not against Mycobacterium avium, Mycobacterium smegmatis, Staphylococcus aureus or Escherichia coli. Importantly, OCT313HK was also effective against MTB clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Interestingly, OCT313HK was exerted the primary bactericidal activity, and it was also exhibited the bacteriolytic activity at high concentrations. We next investigated whether the mycobacterial monooxygenase EthA, a common activator of thiocarbamide-containing antitubercular drugs, also activated OCT313HK. Contrary to our expectations, the anti-tubercular activity of dithiocarbamate sugar derivatives and dithiocarbamates were not dependent on ethA expression, in contrast to thiocarbamide-containing drugs. Overall, this study presents OCT313HK as a novel and potent compound against MTB, particularly promising to overcome drug resistance. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.084
• 作为产物：
  描述：

  吡咯烷二硫代甲酸铵盐 、 2-乙酰氨基-3,4,6-三-O-乙酰-2-脱氧-α-D-吡喃葡萄糖酰基氯 以 丙酮 为溶剂， 反应 0.25h， 以51.4%的产率得到acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl pyrrolidine-1-carbodithioate
  参考文献：
  名称：

  Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives

  摘要：

  The present study was undertaken to optimize the anti-tubercular activity of 2-acetamido-2-deoxy-beta-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313, Glc-NAc-DMDC), a lead compound previously reported by us. Structural modifications of OCT313 included the replacements of the DMDC group at C-1 by pyrrolidine dithiocarbamate (PDTC) and the acetyl group at C-2 by either propyl, butyl, benzyl or oleic acid groups. The antimycobacterial activities of these derivatives were evaluated against Mycobacterium tuberculosis (MTB). Glc-NAc-pyrrolidine dithiocarbamate (OCT313HK, Glc-NAc-PDTC) exhibited the most potent anti-tubercular activity with the minimal inhibitory concentration (MIC) of 6.25-12.5 mu g/ml. The antibacterial activity of OCT313HK was highly specific to MTB and Mycobacterium bovis BCG, but not against Mycobacterium avium, Mycobacterium smegmatis, Staphylococcus aureus or Escherichia coli. Importantly, OCT313HK was also effective against MTB clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Interestingly, OCT313HK was exerted the primary bactericidal activity, and it was also exhibited the bacteriolytic activity at high concentrations. We next investigated whether the mycobacterial monooxygenase EthA, a common activator of thiocarbamide-containing antitubercular drugs, also activated OCT313HK. Contrary to our expectations, the anti-tubercular activity of dithiocarbamate sugar derivatives and dithiocarbamates were not dependent on ethA expression, in contrast to thiocarbamide-containing drugs. Overall, this study presents OCT313HK as a novel and potent compound against MTB, particularly promising to overcome drug resistance. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.084