4-[[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]amino]-4-oxobutanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]amino]-4-oxobutanoic acid
• 化学式: C₁₃H₁₆N₂O₇
• 分子量: 312.279
• InChiKey: VFAMVSYUKUIFGL-ZWNOBZJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]amino]-4-oxobutanoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N¹-(4-aminobutyl)-N⁴-((1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)-propan-2-yl)succinamide trifluoroacetate
  参考文献：
  名称：

  Synthesis and antimicrobial activity of chloramphenicol–polyamine conjugates

  摘要：

  A series of chloramphenicol (CAM) amides with polyamines (PAs), suitable for structure-activity relationship studies, were synthesized either by direct attachment of the PA chain on the 2-aminopropane- 1,3-diol backbone of CAM, previously oxidized selectively at its primary hydroxyl group, or from chloramphenicol base (CLB) through acylation with succinic or phthalic anhydride and finally coupling with a PA. Conjugates 4 and 5, in which the CLB moiety was attached on N4 and N1 positions, respectively, of the N-8,N-8-dibenzylated spermidine through the succinate linker, were the most potent antibacterial agents. Both conjugates were internalized into Escherichia coli cells by using the spermidine-preferential uptake system and caused decrease in protein and polyamine content of the cells. Noteworthy, conjugate 4 displayed comparable activity to CAM in MRSA or wild-type strains of Staphylococcus aureus and Escherichia coli, but superior activity in E. coli strains possessing ribosomal mutations or expressing the CAM acetyltransferase (cat) gene. Lead compounds, and in particular conjugate 4, have been therefore discovered during the course of the present work with clinical potential. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.069
• 作为产物：
  描述：

  丁二酸酐 、 (1R,2R)-2-氨基-1-(4-硝基苯基)丙烷-1,3-二醇 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 4-[[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]amino]-4-oxobutanoic acid
  参考文献：
  名称：

  Synthesis and antimicrobial activity of chloramphenicol–polyamine conjugates

  摘要：

  A series of chloramphenicol (CAM) amides with polyamines (PAs), suitable for structure-activity relationship studies, were synthesized either by direct attachment of the PA chain on the 2-aminopropane- 1,3-diol backbone of CAM, previously oxidized selectively at its primary hydroxyl group, or from chloramphenicol base (CLB) through acylation with succinic or phthalic anhydride and finally coupling with a PA. Conjugates 4 and 5, in which the CLB moiety was attached on N4 and N1 positions, respectively, of the N-8,N-8-dibenzylated spermidine through the succinate linker, were the most potent antibacterial agents. Both conjugates were internalized into Escherichia coli cells by using the spermidine-preferential uptake system and caused decrease in protein and polyamine content of the cells. Noteworthy, conjugate 4 displayed comparable activity to CAM in MRSA or wild-type strains of Staphylococcus aureus and Escherichia coli, but superior activity in E. coli strains possessing ribosomal mutations or expressing the CAM acetyltransferase (cat) gene. Lead compounds, and in particular conjugate 4, have been therefore discovered during the course of the present work with clinical potential. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.069