1,3,2’-triazidoparomamine | 289505-10-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,3,2’-triazidoparomamine
• 英文别名: (2R,3S,4R,5R,6S)-5-azido-6-(((1R,2R,3S,4R,6S)-4, 6-diazido-2,3-dihydroxycyclohexyl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diol；(2R,3S,4R,5R,6S)-5-azido-6-[(1R,2R,3S,4R,6S)-4,6-diazido-2,3-dihydroxycyclohexyl]oxy-2-(hydroxymethyl)oxane-3,4-diol
• CAS: 289505-10-8
• 化学式: C₁₂H₁₉N₉O₇
• 分子量: 401.339
• InChiKey: PQEDVZQKOFIVHS-HKEUSBCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  163
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  1,3,2’-triazidoparomamine 在 sodium hydroxide 、 camphor-10-sulfonic acid 、 三氟化硼乙醚 、 溶剂黄146 、 甲胺 、 三甲基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3R,4S,5R)-2-[(2S,3R,4R,5S,6R)-3-amino-2-[(1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxycyclohexyl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-5-(hydroxymethyl)oxolane-3,4-diol
  参考文献：
  名称：

  Redesign of aminoglycosides for treatment of human genetic diseases caused by premature stop mutations

  摘要：

  A series of new derivatives of the clinically used aminoglycoside antibiotic paromomycin were designed, synthesized, and their ability to read-through premature stop codon mutations was examined in both in vitro translation system and ex vivo mammalian cultured cells. One of these structures, a pseudo-trisaccharide derivative, showed notably higher stop codon read-through activity in cultured cells compared to those of paromomycin and gentamicin. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.013
• 作为产物：
  描述：

  paromomycin sulfate 在 甲醇 、 copper(ll) sulfate pentahydrate 、 triflic azide 、 三乙胺 、 乙酰氯 作用下， 生成 1,3,2’-triazidoparomamine
  参考文献：
  名称：

  迈向催化抗生素：氨基糖苷的重新设计以催化禁用细菌核糖体。

  摘要：

  催化抗生素的作用：提出了一种新霉素B衍生物对核糖体RNA解码位点中G1491和A1492之间的磷酸二酯键水解的催化作用的模式。在新霉素B的4'-位连接的乙二胺部分充当催化核弹头，通过酸碱催化裂解磷酸二酯键。

  DOI：

  10.1002/cbic.201800549

文献信息

• Novel aminoglycosides and uses thereof in the treatment of genetic disorders
  申请人：Bassov Timor

  公开号：US20090093418A1

  公开（公告）日：2009-04-09

  A new class of paromomycin-derived aminoglycosides, which exhibit efficient stop-codon mutation suppression activity, low toxicity and high selectivity towards eukaryotic cells are provided. Also provided are chemical and chemo-enzymatic processes of preparing these paromomycin-derived aminoglycosides and intermediates thereof, as well as pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders.

  提供了一类新型的巴罗霉素衍生氨基糖苷类化合物，具有高效的终止密码子突变抑制活性、低毒性和高选择性作用于真核细胞。同时提供了制备这些巴罗霉素衍生氨基糖苷类化合物及其中间体的化学和化酶过程，以及含有它们的药物组合物，并在遗传疾病治疗中的应用。
• Synthesis of 4′-deoxy-4′-fluoro neamine and 4′-deoxy-4′-fluoro 4′-<i>epi</i>neamine
  作者：Stephen Hanessian、Oscar M. Saavedra、Miguel A. Vilchis-Reyes、Ana M. Llaguno-Rueda

  DOI：10.1039/c4md00072b

  日期：——

  The syntheses of 4′-deoxy-4′-fluoro neamine and 4′-deoxy-4′-fluoro 4′-epineamine from the readily available neamine and paromamine are described.

  描述了从易得的neamine和paromamine合成4'-去氧-4'-氟奈胺和4'-去氧-4'-氟4'-epi奈胺的方法。
• Efficient synthesis of neomycin B related aminoglycosides
  作者：Yili Ding、Eric E Swayze、Steven A Hofstadler、Richard H Griffey

  DOI：10.1016/s0040-4039(00)00586-4

  日期：2000.5

  Aminoglycosides 6′-hydroxyl-ribostamycin and 5-(α-neobiosamine)-2-deoxystreptamine were chemically synthesized. These compounds will be used as standards to compare RNA binding affinity and specificity with neomycin B.

  化学合成了氨基糖苷类6'-羟基-核糖霉素和5-（α-新烟酰胺）-2-脱氧链胺胺。这些化合物将用作比较新霉素B与RNA结合的亲和力和特异性的标准。
• Exploring eukaryotic <i>versus</i> prokaryotic ribosomal RNA recognition with aminoglycoside derivatives
  作者：Narayana Murthy Sabbavarapu、Tomasz Pieńko、Bat-Hen Zalman、Joanna Trylska、Timor Baasov

  DOI：10.1039/c8md00001h

  日期：——

  ability to readthrough nonsense mutations was examined in vitro, along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure–activity relationships, along with the comparative molecular dynamics simulations within the eukaryotic rRNA decoding site, showed high sensitivity of 6′-position to substitution, indicating that the rational design of potent stop-codon

  设计、合成了在其环 I 上含有 6'-羧酸或 6'-酰胺的氨基糖苷类的新衍生物，并在体外检测了它们读取无义突变的能力，以及在原核和真核系统中的蛋白质翻译抑制。观察到的结构-活性关系，以及真核 rRNA 解码位点内的比较分子动力学模拟，显示出 6' 位对取代的高度敏感性，表明有效的终止密码子通读诱导剂的合理设计需要考虑不只有药物-RNA相互作用的结构和能量学，还有与这种相互作用相关的动力学。
• Design of Novel Aminoglycoside Derivatives with Enhanced Suppression of Diseases-Causing Nonsense Mutations
  作者：Narayana Murthy Sabbavarapu、Michal Shavit、Yarden Degani、Boris Smolkin、Valery Belakhov、Timor Baasov

  DOI：10.1021/acsmedchemlett.6b00006

  日期：2016.4.14

  New pseudotrisaccharide derivatives of aminoglycosides that exploit additional interaction on the shallow groove face of the decoding-site rRNA of eukaryotic ribosome were designed, synthesized and biologically evaluated. Novel lead structures (6 and 7 with an additional 7'-OH), exhibiting enhanced specificity to eukaryotic cytoplasmic ribosome, and superior nonsense mutation suppression activity than those of gentamicin, were discovered. The comparative benefit of new leads was demonstrated in four different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Usher syndrome, and Hurler syndrome.