6',3-N,N-bis(tert-butyloxycarrbonyl)kanamycin A | 75178-77-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6',3-N,N-bis(tert-butyloxycarrbonyl)kanamycin A
• 英文别名: Boc-protected Kanamycin A d8-Major；tert-butyl N-[[(2R,3S,4S,5R,6R)-6-[(1R,2R,3S,4R,6S)-4-amino-3-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxy-6-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexyl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl]carbamate
• CAS: 75178-77-7
• 化学式: C₂₈H₅₂N₄O₁₅
• 分子量: 684.739
• InChiKey: UINNIZSDURJEBV-OSMKSXLKSA-N

物化性质

• 沸点：
  904.2±65.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  307
• 氢给体数：
  11
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  6',3-N,N-bis(tert-butyloxycarrbonyl)kanamycin A 在 四氢呋喃 、 盐酸 、 copper diacetate 作用下， 反应 30.0h， 生成
  参考文献：
  名称：

  Synthesis and Antimicrobial and Toxicological Studies of Amino Acid and Peptide Derivatives of Kanamycin A and Netilmicin

  摘要：

  Amino acid and peptide derivatives of aminoglycosides have been obtained by substitution of the 1-N or 6'-N amino functions of kanamycin A and netilmicin via the temporary complexation of vicinal and nonvicinal amino and hydroxy functions by copper ion [1-N kanamycin A derivatives: L-Ala(Ga), D-Ala (6b), Gly (6c), L-Asp (6d), L-Ala-L-Ala (6e). 6'-N kanamycin A derivatives: L-Ala (3a), D-Ala (3b), Gly (3c), L-Ala-L-Ala (3e), L-Leu (3f). 6'-N netilmicin derivatives: L-Ala(9a), D-Ala (9b), Gly (9c), L-Asp (9d), L-Ala-L-Ala (9e)]. Characterization was made by FAB-MS, IR, H-1-NMR, and C-13-NMR. All derivatives were essentially inactive. The nephrotoxic potential of the derivatives obtained in sufficient quantities (3b,e and 9a-e) was assessed by measuring their inhibitory potential toward the activity of lysosomal phospholipase A(1) acting on phosphatidylcholine embedded in negatively-charged membranes. One compound, 6'-N-L-Ala-netilmicin (9a), showed a a-fold decrease of inhibitory potency compared to its parent drug. A conformational analysis revealed that it adopts two equally probable conformations and orientations when interacting with phosphatidylinositol. The first in which the drug lies parallel to the hydrophobic-hydrophilic interface, is similar to that of netilmicin. The second, in which the drug inserts itself in the bilayer across the hydrophilic/hydrophobic interface, is similar to that described for streptomycin, an almost non-nephrotoxic aminoglycoside.

  DOI：

  10.1021/jm00023a011
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 卡那霉素碱 在 copper dichloride 作用下， 生成 6',3-N,N-bis(tert-butyloxycarrbonyl)kanamycin A
  参考文献：
  名称：

  Synthesis and Antimicrobial and Toxicological Studies of Amino Acid and Peptide Derivatives of Kanamycin A and Netilmicin

  摘要：

  Amino acid and peptide derivatives of aminoglycosides have been obtained by substitution of the 1-N or 6'-N amino functions of kanamycin A and netilmicin via the temporary complexation of vicinal and nonvicinal amino and hydroxy functions by copper ion [1-N kanamycin A derivatives: L-Ala(Ga), D-Ala (6b), Gly (6c), L-Asp (6d), L-Ala-L-Ala (6e). 6'-N kanamycin A derivatives: L-Ala (3a), D-Ala (3b), Gly (3c), L-Ala-L-Ala (3e), L-Leu (3f). 6'-N netilmicin derivatives: L-Ala(9a), D-Ala (9b), Gly (9c), L-Asp (9d), L-Ala-L-Ala (9e)]. Characterization was made by FAB-MS, IR, H-1-NMR, and C-13-NMR. All derivatives were essentially inactive. The nephrotoxic potential of the derivatives obtained in sufficient quantities (3b,e and 9a-e) was assessed by measuring their inhibitory potential toward the activity of lysosomal phospholipase A(1) acting on phosphatidylcholine embedded in negatively-charged membranes. One compound, 6'-N-L-Ala-netilmicin (9a), showed a a-fold decrease of inhibitory potency compared to its parent drug. A conformational analysis revealed that it adopts two equally probable conformations and orientations when interacting with phosphatidylinositol. The first in which the drug lies parallel to the hydrophobic-hydrophilic interface, is similar to that of netilmicin. The second, in which the drug inserts itself in the bilayer across the hydrophilic/hydrophobic interface, is similar to that described for streptomycin, an almost non-nephrotoxic aminoglycoside.

  DOI：

  10.1021/jm00023a011