N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide | 1092494-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide
• 英文别名: benzyl [(1S,2R,6S,7R)-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl] carbonate
• CAS: 1092494-97-7
• 化学式: C₁₇H₁₅NO₅
• 分子量: 313.31
• InChiKey: SSVLHTOYYHGIND-KPWCQOOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide 在 copper diacetate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 生成 1,2',6'-tri-N-(tert-butoxycarbonyl)-3-N-carbobenzyloxyneamine
  参考文献：
  名称：

  Loss of individual electrostatic interactions between aminoglycoside antibiotics and resistance enzymes as an effective means to overcoming bacterial drug resistance

  摘要：

  Aminoglycoside-modifying enzymes modify the structures of aminoglycoside antibiotics, rendering them ineffective, a process which confers resistance to the antibiotic. Electrostatic interactions (ion pairing and hydrogen bonding) are believed to be significant for both substrate recognition and catalysis by these enzymes. Regiospecific syntheses of seven distinct deaminated analogues of neamine and kanamycin A, two aminoglycoside antibiotics, are described. Each of these compounds would have impaired interaction with a different subsite of the enzyme active sites. All seven molecules were shown to be exceedingly poor substrates for two aminoglycoside-modifying enzymes, aminoglycoside 3'-phosphotransferases types Ia and IIa. The energetic contribution of interactions of the active-site functions with each of these amines on stabilization of the transition-state species has been evaluated to be in the range of 6-11 kcal/mol, the largest energy contribution recorded in the literature for such interactions. The biological activities of these analogues were the same against the resistant organisms harboring aminoglycoside 3'-phosphotransferases types Ia and IIa as those against the background strain without the resistant enzymes. Thus, these compounds are virtually unmodified by those enzymes in vivo. The principles described here should be of general interest for circumvention of resistance to other antibiotics, by redesigning the electrostatic interactions with their corresponding resistance enzymes.

  DOI：

  10.1021/ja00150a004
• 作为产物：
  描述：

  endo-N-Hydroxy-5-norbornene-2,3-dicarboximide 、 氯甲酸苄酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以93%的产率得到N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide
  参考文献：
  名称：

  含磺酰胺，亚砜或砜的氨基糖苷-CoA双底物的合成和用途，作为氨基糖苷N-6'-乙酰基转移酶的机械探针。

  摘要：

  氨基糖苷-辅酶A共轭物因具有丰富的官能团和起始原料的高极性而成为具有挑战性的合成靶标。我们以前报道过一锅法合成酰胺连接的氨基糖苷-CoA双底物。这些分子是氨基糖苷N-6'-乙酰基转移酶Ii（AAC（6'）-Ii）的纳摩尔抑制剂，这是一种对细菌对氨基糖苷抗生素具有抗性的重要酶。我们在这里报告了五个新的包含磺酰胺，亚砜或砜基团的氨基糖苷-CoA双底物的合成和生物活性。有趣的是，与酰胺连接的双底物相比，预期最能模仿四面体中间体的磺酰胺连接的双底物没有显示出改善的抑制作用。另一方面，

  DOI：

  10.1016/j.bmcl.2008.09.004

文献信息

• Conjoint molecules of cephalosporins and aminoglycosides
  作者：Ioannis Grapsas、Stephen A. Lerner、Shahriar Mobashery

  DOI：10.1002/1521-4184(200109)334:8/9<295::aid-ardp295>3.0.co;2-3

  日期：2001.9

  A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial beta -lactamases, enzymes that hydrolyze the beta -lactam bond of cephalosporins. Hydrolysis of the beta -lactam bond was expected to release the Clo-appended aminoglycoside. Since beta -lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.
• Synthesis and use of sulfonamide-, sulfoxide-, or sulfone-containing aminoglycoside–CoA bisubstrates as mechanistic probes for aminoglycoside N-6′-acetyltransferase
  作者：Feng Gao、Xuxu Yan、Omar Zahr、Aaron Larsen、Kenward Vong、Karine Auclair

  DOI：10.1016/j.bmcl.2008.09.004

  日期：2008.10

  Aminoglycoside-coenzyme A conjugates are challenging synthetic targets because of the wealth of functional groups and high polarity of the starting materials. We previously reported a one-pot synthesis of amide-linked aminoglycoside-CoA bisubstrates. These molecules are nanomolar inhibitors of aminoglycoside N-6'-acetyltransferase Ii (AAC(6')-Ii), an important enzyme involved in bacterial resistance

  氨基糖苷-辅酶A共轭物因具有丰富的官能团和起始原料的高极性而成为具有挑战性的合成靶标。我们以前报道过一锅法合成酰胺连接的氨基糖苷-CoA双底物。这些分子是氨基糖苷N-6'-乙酰基转移酶Ii（AAC（6'）-Ii）的纳摩尔抑制剂，这是一种对细菌对氨基糖苷抗生素具有抗性的重要酶。我们在这里报告了五个新的包含磺酰胺，亚砜或砜基团的氨基糖苷-CoA双底物的合成和生物活性。有趣的是，与酰胺连接的双底物相比，预期最能模仿四面体中间体的磺酰胺连接的双底物没有显示出改善的抑制作用。另一方面，
• Loss of individual electrostatic interactions between aminoglycoside antibiotics and resistance enzymes as an effective means to overcoming bacterial drug resistance
  作者：Juliatiek Roestamadji、Ioannis Grapsas、Shahriar Mobashery

  DOI：10.1021/ja00150a004

  日期：1995.11

  Aminoglycoside-modifying enzymes modify the structures of aminoglycoside antibiotics, rendering them ineffective, a process which confers resistance to the antibiotic. Electrostatic interactions (ion pairing and hydrogen bonding) are believed to be significant for both substrate recognition and catalysis by these enzymes. Regiospecific syntheses of seven distinct deaminated analogues of neamine and kanamycin A, two aminoglycoside antibiotics, are described. Each of these compounds would have impaired interaction with a different subsite of the enzyme active sites. All seven molecules were shown to be exceedingly poor substrates for two aminoglycoside-modifying enzymes, aminoglycoside 3'-phosphotransferases types Ia and IIa. The energetic contribution of interactions of the active-site functions with each of these amines on stabilization of the transition-state species has been evaluated to be in the range of 6-11 kcal/mol, the largest energy contribution recorded in the literature for such interactions. The biological activities of these analogues were the same against the resistant organisms harboring aminoglycoside 3'-phosphotransferases types Ia and IIa as those against the background strain without the resistant enzymes. Thus, these compounds are virtually unmodified by those enzymes in vivo. The principles described here should be of general interest for circumvention of resistance to other antibiotics, by redesigning the electrostatic interactions with their corresponding resistance enzymes.