1,3,2',6'-tetra-N-benzyl-3'-O-(7''-bromoheptyl)-1,3,2'-tri-N-tert-butoxycarbonyl-6'-N,4'-O-carbonyl-5,6-O-cyclohexylideneneamine | 312957-59-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,3,2',6'-tetra-N-benzyl-3'-O-(7''-bromoheptyl)-1,3,2'-tri-N-tert-butoxycarbonyl-6'-N,4'-O-carbonyl-5,6-O-cyclohexylideneneamine
• 英文别名: tert-butyl N-[(3aS,4R,5S,7R,7aS)-4-[[(4aR,6R,7R,8R,8aR)-3-benzyl-7-[benzyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-8-(7-bromoheptoxy)-2-oxo-4,4a,6,7,8,8a-hexahydropyrano[2,3-e][1,3]oxazin-6-yl]oxy]-7-[benzyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]spiro[3a,4,5,6,7,7a-hexahydro-1,3-benzodioxole-2,1'-cyclohexane]-5-yl]-N-benzylcarbamate
• CAS: 312957-59-8
• 化学式: C₆₉H₉₃BrN₄O₁₃
• 分子量: 1266.42
• InChiKey: FITOLUHZBWCQFO-RGMFOWNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.7
• 重原子数：
  87
• 可旋转键数：
  27
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  164
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  N6-苯甲酰基-2',3'-O-异丙亚基腺苷 、 1,3,2',6'-tetra-N-benzyl-3'-O-(7''-bromoheptyl)-1,3,2'-tri-N-tert-butoxycarbonyl-6'-N,4'-O-carbonyl-5,6-O-cyclohexylideneneamine 在 氢氧化钾 、 四丁基碘化铵 作用下， 以 吡啶 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Tethered Bisubstrate Derivatives as Probes for Mechanism and as Inhibitors of Aminoglycoside 3‘-Phosphotransferases

  摘要：

  Aminoglycoside 3'-phosphotransferases [APH(3')s] phosphorylate aminoglycoside antibiotics, a reaction that inactivates the antibiotics. These enzymes are the primary cause of resistance to aminoglycosides in bacteria. APH(3')-Ia operates by a random-equilibrium BiBi mechanism, whereas APH(3')-IIIa catalyzes its reaction by the Theorell-Chance mechanism, a form of ordered BiBi mechanism. Hence, both substrates have to be present in the active site prior to the transfer of phosphate by both mechanisms. Four bisubstrate analogues, compounds 1-4, were designed and synthesized as inhibitors for APH(3')s. These compounds are made of adenosine linked covalently to the 3'-hydroxyl of neamine (an aminoglycoside) via all-methylene tethers of 5-8 carbons. The K-i values measured for these compounds indicated that affinities of APH(3')-Ia and APH(3')-IIa for compounds 2 and 3 (six- and seven-carbon tethers, respectively) were the best, and the inhibition constants for the two were comparable.

  DOI：

  10.1021/jo000589k
• 作为产物：
  描述：

  neamine tetrahydrochloride 在 咪唑 、 氢氧化钾 、 四丁基氟化铵 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.67h， 生成 1,3,2',6'-tetra-N-benzyl-3'-O-(7''-bromoheptyl)-1,3,2'-tri-N-tert-butoxycarbonyl-6'-N,4'-O-carbonyl-5,6-O-cyclohexylideneneamine
  参考文献：
  名称：

  Tethered Bisubstrate Derivatives as Probes for Mechanism and as Inhibitors of Aminoglycoside 3‘-Phosphotransferases

  摘要：

  Aminoglycoside 3'-phosphotransferases [APH(3')s] phosphorylate aminoglycoside antibiotics, a reaction that inactivates the antibiotics. These enzymes are the primary cause of resistance to aminoglycosides in bacteria. APH(3')-Ia operates by a random-equilibrium BiBi mechanism, whereas APH(3')-IIIa catalyzes its reaction by the Theorell-Chance mechanism, a form of ordered BiBi mechanism. Hence, both substrates have to be present in the active site prior to the transfer of phosphate by both mechanisms. Four bisubstrate analogues, compounds 1-4, were designed and synthesized as inhibitors for APH(3')s. These compounds are made of adenosine linked covalently to the 3'-hydroxyl of neamine (an aminoglycoside) via all-methylene tethers of 5-8 carbons. The K-i values measured for these compounds indicated that affinities of APH(3')-Ia and APH(3')-IIa for compounds 2 and 3 (six- and seven-carbon tethers, respectively) were the best, and the inhibition constants for the two were comparable.

  DOI：

  10.1021/jo000589k

文献信息

• Tethered Bisubstrate Derivatives as Probes for Mechanism and as Inhibitors of Aminoglycoside 3‘-Phosphotransferases
  作者：Meizheng Liu、Jalal Haddad、Eduardo Azucena、Lakshmi P. Kotra、Maria Kirzhner、Shahriar Mobashery

  DOI：10.1021/jo000589k

  日期：2000.11.1

  Aminoglycoside 3'-phosphotransferases [APH(3')s] phosphorylate aminoglycoside antibiotics, a reaction that inactivates the antibiotics. These enzymes are the primary cause of resistance to aminoglycosides in bacteria. APH(3')-Ia operates by a random-equilibrium BiBi mechanism, whereas APH(3')-IIIa catalyzes its reaction by the Theorell-Chance mechanism, a form of ordered BiBi mechanism. Hence, both substrates have to be present in the active site prior to the transfer of phosphate by both mechanisms. Four bisubstrate analogues, compounds 1-4, were designed and synthesized as inhibitors for APH(3')s. These compounds are made of adenosine linked covalently to the 3'-hydroxyl of neamine (an aminoglycoside) via all-methylene tethers of 5-8 carbons. The K-i values measured for these compounds indicated that affinities of APH(3')-Ia and APH(3')-IIa for compounds 2 and 3 (six- and seven-carbon tethers, respectively) were the best, and the inhibition constants for the two were comparable.