6''-deoxy-6''-(N-butyryl-N-methylamino)kanamycin B | 132102-55-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6''-deoxy-6''-(N-butyryl-N-methylamino)kanamycin B
• 英文别名: N-[[(2R,3S,4S,5R,6R)-4-amino-6-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,4R,5S,6R)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-3,5-dihydroxyoxan-2-yl]methyl]-N-methylbutanamide
• CAS: 132102-55-7
• 化学式: C₂₃H₄₆N₆O₁₀
• 分子量: 566.652
• InChiKey: HEWXMOCBWUXKAH-FEZUQLPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.7
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  289
• 氢给体数：
  10
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 1.05h， 生成 6''-deoxy-6''-(N-butyryl-N-methylamino)kanamycin B
  参考文献：
  名称：

  New derivatives of kanamycin B obtained by modifications and substitutions in position 6''. 1. Synthesis and microbiological evaluation

  摘要：

  The clinical use of the potent, wide-spectrum aminoglycoside antibiotics is limited by oto- and nephrotoxicities. The latter is related to the binding of these polycationic drugs to negatively charged phospholipids and to the subsequent inhibition of lysosomal phospholipases. In order to explore the influence of a modification of the hydrophobic/hydrophilic balance at a specific site of an aminoglycoside, kanamycin B has been chemically modified in position 6" by substitution of the hydroxyl group with a halogen atom (or a pseudohalogen group), or an amino, an amido, a thioalkyl, or an alkoxy group, each series containing increasingly bulkier chains. Examination of the antibacterial activity of the synthesized compounds revealed a negative correlation between the size of the 6"-substituent and the antibacterial activity against kanamycin B sensitive Gram-positive and -negative organisms. Only derivatives with small substituents in position 6", namely chloro, bromo, azido, amino, methylcarbamido, acetamido, methylthio, methylsulfinyl, O-methyl, O-ethyl, and O-isopropyl, showed acceptable activity (geometric mean of minimum inhibitory concentrations for Gram-negative strains less-than-or-equal-to 2.5 mg/L; value for kanamycin B, 0.5 mg/L). In vitro toxicological evaluation of all derivatives and computer-aided conformational analysis of selected compounds inserted in a phosphatidylinositol monolayer are presented in the following paper in this issue.

  DOI：

  10.1021/jm00108a035

文献信息

• New derivatives of kanamycin B obtained by modifications and substitutions in position 6''. 1. Synthesis and microbiological evaluation
  作者：A. Van Schepdael、J. Delcourt、M. Mulier、R. Busson、L. Verbist、H. J. Vanderhaeghe、M. P. Mingeot-Leclercq、P. M. Tulkens、P. J. Claes

  DOI：10.1021/jm00108a035

  日期：1991.4

  The clinical use of the potent, wide-spectrum aminoglycoside antibiotics is limited by oto- and nephrotoxicities. The latter is related to the binding of these polycationic drugs to negatively charged phospholipids and to the subsequent inhibition of lysosomal phospholipases. In order to explore the influence of a modification of the hydrophobic/hydrophilic balance at a specific site of an aminoglycoside, kanamycin B has been chemically modified in position 6" by substitution of the hydroxyl group with a halogen atom (or a pseudohalogen group), or an amino, an amido, a thioalkyl, or an alkoxy group, each series containing increasingly bulkier chains. Examination of the antibacterial activity of the synthesized compounds revealed a negative correlation between the size of the 6"-substituent and the antibacterial activity against kanamycin B sensitive Gram-positive and -negative organisms. Only derivatives with small substituents in position 6", namely chloro, bromo, azido, amino, methylcarbamido, acetamido, methylthio, methylsulfinyl, O-methyl, O-ethyl, and O-isopropyl, showed acceptable activity (geometric mean of minimum inhibitory concentrations for Gram-negative strains less-than-or-equal-to 2.5 mg/L; value for kanamycin B, 0.5 mg/L). In vitro toxicological evaluation of all derivatives and computer-aided conformational analysis of selected compounds inserted in a phosphatidylinositol monolayer are presented in the following paper in this issue.