tert-butyl N-[(2R,3R,4R,5S,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-4,5-dihydroxy-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-3-yl]carbamate | 54230-38-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl N-[(2R,3R,4R,5S,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-4,5-dihydroxy-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-3-yl]carbamate
• CAS: 54230-38-5
• 化学式: C₃₈H₆₆N₄O₁₄
• 分子量: 802.96
• InChiKey: YJQGENKZYJSAQK-DZEZIBHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  56
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  231
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2R,3R,4R,5S,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-4,5-dihydroxy-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-3-yl]carbamate 在 咪唑 、 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 三乙胺 作用下， 生成 tert-butyl N-[(2R,3R,4R,5S,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-4,5-dihydroxy-6-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]oxan-3-yl]carbamate
  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

• miRNA PROCESSING INHIBITOR EFFICACY ASSAYS AND SUBSTANCES
  申请人：Arenz Christoph

  公开号：US20090092980A1

  公开（公告）日：2009-04-09

  The invention relates to assays for assessing miRNA maturation effector (preferably: inhibitor) efficacy, and to substances useful for influencing, particularly for inhibiting, maturation of miRNA. According to the invention there is provided assay of miRNA processing inhibitor efficacy, comprising the steps of: a) providing a target miRNA precursor, b) providing a potential inhibitor of one or more processing steps of the target miRNA precursor, c) bringing together of the target miRNA precursor and the potential inhibitor under miRNA maturation conditions, and d) determining inhibition efficiency. The assay of the present invention allows for a very fast and easy assessment of the efficacy of a potential inhibitor in inhibiting processing of a miRNA precursor into miRNA.

  该发明涉及用于评估miRNA成熟效应子（优选：抑制剂）效力的检测方法，以及用于影响miRNA成熟的物质，特别是用于抑制miRNA成熟的物质。根据该发明提供了miRNA处理抑制剂效力的检测方法，包括以下步骤：a）提供目标miRNA前体，b）提供一个或多个目标miRNA前体处理步骤的潜在抑制剂，c）在miRNA成熟条件下将目标miRNA前体和潜在抑制剂结合在一起，d）确定抑制效率。本发明的检测方法允许非常快速和简便地评估潜在抑制剂在抑制miRNA前体转化为miRNA的处理过程中的效力。
• 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.