6'-N-benzyloxycarbonyltobramycin

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6'-N-benzyloxycarbonyltobramycin
• 英文别名: Tobramycin N-Benzylcarbamate；benzyl N-[[(2R,3S,5R,6R)-5-amino-6-[(1R,2S,3S,4R,6S)-4,6-diamino-3-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-3-hydroxyoxan-2-yl]methyl]carbamate
• 化学式: C₂₆H₄₃N₅O₁₁
• 分子量: 601.654
• InChiKey: BEXIVPCNIMMKTH-BMKNFZGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  281
• 氢给体数：
  10
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  6'-N-benzyloxycarbonyltobramycin 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 生成 1,3,2',3''-tetra-N-acetyltobramycin
  参考文献：
  名称：

  Microscopic protonation constants in tobramycin. An NMR and pH study with the aid of partially N-acetylated derivatives

  摘要：

  Three tetra-N-acetyl derivatives and one tri-N-acetyl derivative of tobramycin (1) have been prepared by partial N-acetylation. Comparison of the pK(a) values, determined by NMR chemical shift titrations and pH titration of the derivatives, with those of unprotected 1 suggests that protonation equilibria at any particular amino group in 1 are not likely to be influenced by those at other sites. pH-Dependent conformational changes in 1 were assessed on the basis of H-1 and C-13 chemical shift changes in the derivatives.

  DOI：

  10.1016/0008-6215(93)84244-z
• 作为产物：
  描述：

  尼拉霉素 、 氯甲酸苄酯 在 1-羟基苯并三唑 、 三乙胺 作用下， 生成 6'-N-benzyloxycarbonyltobramycin
  参考文献：
  名称：

  Microscopic protonation constants in tobramycin. An NMR and pH study with the aid of partially N-acetylated derivatives

  摘要：

  Three tetra-N-acetyl derivatives and one tri-N-acetyl derivative of tobramycin (1) have been prepared by partial N-acetylation. Comparison of the pK(a) values, determined by NMR chemical shift titrations and pH titration of the derivatives, with those of unprotected 1 suggests that protonation equilibria at any particular amino group in 1 are not likely to be influenced by those at other sites. pH-Dependent conformational changes in 1 were assessed on the basis of H-1 and C-13 chemical shift changes in the derivatives.

  DOI：

  10.1016/0008-6215(93)84244-z

文献信息

• Design of Ionizable Lipids To Overcome the Limiting Step of Endosomal Escape: Application in the Intracellular Delivery of mRNA, DNA, and siRNA
  作者：Damien Habrant、Pauline Peuziat、Thibault Colombani、Laurence Dallet、Johan Gehin、Emilie Goudeau、Bérangère Evrard、Olivier Lambert、Thomas Haudebourg、Bruno Pitard

  DOI：10.1021/acs.jmedchem.5b01679

  日期：2016.4.14

  The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from naturally occurring aminoglycoside tobramycin, was prepared using improved synthetic

  核酸分子的细胞内递送是一个复杂的过程，涉及几个不同的步骤。其中，对于有效地向宿主细胞中产生蛋白质（或抑制），内体逃逸似乎尤为重要。在本研究中，使用改良的合成程序制备了一系列新的可离子化的载体，这些载体均来自天然存在的氨基糖苷妥布霉素，可在接头和疏水域上进行结构变化。新的可电离脂质与mRNA，DNA或siRNA之间形成的复合物通过冷冻TEM实验进行了表征，并使用不同的细胞类型评估了它们的转染能力。我们证明了铅分子30，带有可生物降解的二酯连接子，与核酸形成小的复合物，并且对所有测试的核酸和细胞类型均具有非常高的转染效率。获得的结果表明，通过脂质混合机制优化的内体逃逸，可改善30种“通用”递送特性。
• Synthesis and Biological Activity of Mono- and Di-<i>N</i>-acylated Aminoglycosides
  作者：Nishad Thamban Chandrika、Keith D. Green、Jacob L. Houghton、Sylvie Garneau-Tsodikova

  DOI：10.1021/acsmedchemlett.5b00255

  日期：2015.11.12

  Despite issues with oto/nephrotoxicity and bacterial resistance, aminoglycosides (AGs) remain an effective and widely used class of antibacterial agents. For decades now, efforts toward the development of novel AGs with potential to overcome some of these problems have been major research focuses. 1-N-Acylation, especially gamma-amino-beta-hydroxybutyrate (AHB) derivatization, has proven to be one of the most successful strategies for improving the overall properties of AGs, including their ability to avoid certain resistance mechanisms. More recently, 6'-N-acylation arose as another possible strategy to improve the properties of these drugs. In this study, we report on the glycinyl, carboxybenzyl, and AHB mono- and diderivatization at the 1-, 6'-, and/or 4'''-amines of the AGs amikacin, kanamycin A, netilmicin, sisomicin, and tobramycin. We also present the antibacterial activities and the reduced reactivity of AG-modifying enzymes (AMEs) toward these new AG derivatives, and identify the AMEs present in the bacterial strains tested.
• Microscopic protonation constants in tobramycin. An NMR and pH study with the aid of partially N-acetylated derivatives
  作者：László Szilágyi、Zita Sz. Pusztahelyi、Sándor Jakab、Imre Kovács

  DOI：10.1016/0008-6215(93)84244-z

  日期：1993.9

  Three tetra-N-acetyl derivatives and one tri-N-acetyl derivative of tobramycin (1) have been prepared by partial N-acetylation. Comparison of the pK(a) values, determined by NMR chemical shift titrations and pH titration of the derivatives, with those of unprotected 1 suggests that protonation equilibria at any particular amino group in 1 are not likely to be influenced by those at other sites. pH-Dependent conformational changes in 1 were assessed on the basis of H-1 and C-13 chemical shift changes in the derivatives.