1,3,2',6'-tetra-N-tert-butoxycarbonyl-3'-O-tert-butyldimethylsilyl-5,6-O-cyclohexylideneneamine | 312957-53-2

• 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-tert-butoxycarbonyl-3'-O-tert-butyldimethylsilyl-5,6-O-cyclohexylideneneamine
• 英文别名: tert-butyl N-[(2R,3R,4R,5R,6R)-2-[(3aS,4R,5S,7R,7aS)-5,7-bis[(2-methylpropan-2-yl)oxycarbonylamino]spiro[3a,4,5,6,7,7a-hexahydro-1,3-benzodioxole-2,1'-cyclohexane]-4-yl]oxy-4-[tert-butyl(dimethyl)silyl]oxy-5-hydroxy-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-3-yl]carbamate
• CAS: 312957-53-2
• 化学式: C₄₄H₈₀N₄O₁₄Si
• 分子量: 917.223
• InChiKey: SLMZLGLVRWGFRT-WXCQEDPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  63
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  220
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  1,3,2',6'-tetra-N-tert-butoxycarbonyl-3'-O-tert-butyldimethylsilyl-5,6-O-cyclohexylideneneamine 在 氢氧化钾 、 四丁基氟化铵 、 sodium hydride 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 2.67h， 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
• 作为产物：
  描述：

  neamine tetrahydrochloride 在 咪唑 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1,3,2',6'-tetra-N-tert-butoxycarbonyl-3'-O-tert-butyldimethylsilyl-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

• Short and Efficient Synthesis of Alkyne-Modified Amino Glycoside Building Blocks
  作者：Claudine M. Klemm、Arne Berthelmann、Saskia Neubacher、Christoph Arenz

  DOI：10.1002/ejoc.200900076

  日期：2009.6

  In the light of recent progress in RNA biology, the need for molecules that bind to RNA and thus may be suited to manipulating RNA-mediated processes is steadily increasing. We present a very short and efficient synthetic route to alkyne-modified neamine and 2-deoxystreptamine derivatives on a half-gram scale. These derivatives are suitable for constructing a library of potential divalent RNA binders

  鉴于 RNA 生物学的最新进展，对与 RNA 结合并因此可能适合操纵 RNA 介导过程的分子的需求正在稳步增加。我们提出了一种非常短且有效的合成路线，以半克规模合成炔烃改性的新胺和 2-脱氧链霉胺衍生物。这些衍生物适用于通过铜催化的 1,3-偶极环加成与二叠氮化物（“点击化学”）构建潜在二价 RNA 结合剂库。由此形成的缀合物二聚体抑制 Dicer 介导的微 RNA 成熟，IC50 值介于 0.6 和 15 μM 之间。（© Wiley-VCH Verlag GmbH & Co. KGaA，69451 Weinheim，德国，2009）
• 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.