acetic acid 2-[3-acetoxy-4-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-5-hydroxymethyl-tetrahydro-furan-2-yloxy]-4,6-diazido-3-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-cyclohexyl ester | 620172-08-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: acetic acid 2-[3-acetoxy-4-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-5-hydroxymethyl-tetrahydro-furan-2-yloxy]-4,6-diazido-3-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-cyclohexyl ester
• CAS: 620172-08-9
• 化学式: C₃₅H₄₆N₁₈O₁₉
• 分子量: 1022.86
• InChiKey: PHTSPSWWKYCZDF-PTUCDITASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.64
• 重原子数：
  72.0
• 可旋转键数：
  21.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  525.97
• 氢给体数：
  1.0
• 氢受体数：
  25.0

反应信息

• 作为反应物：
  描述：

  acetic acid 2-[3-acetoxy-4-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-5-hydroxymethyl-tetrahydro-furan-2-yloxy]-4,6-diazido-3-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-cyclohexyl ester 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 甲胺 、 三甲基膦 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 31.0h， 生成 (2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-2-[(2R,3R,4S,5S)-4-[(2R,3R,4R,5S,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-3-hydroxy-5-(sulfanylmethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol
  参考文献：
  名称：

  合成氨基糖苷的双重作用：对炭疽芽孢杆菌的抗菌活性和对炭疽致死因子的抑制作用。

  摘要：

  DOI：

  10.1002/anie.200462003
• 作为产物：
  描述：

  在 氟化氢吡啶 作用下， 以 吡啶 为溶剂， 反应 0.08h， 以93%的产率得到acetic acid 2-[3-acetoxy-4-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-5-hydroxymethyl-tetrahydro-furan-2-yloxy]-4,6-diazido-3-(4,5-diacetoxy-3-azido-6-azidomethyl-tetrahydro-pyran-2-yloxy)-cyclohexyl ester
  参考文献：
  名称：

  A New Class of Branched Aminoglycosides:  Pseudo-Pentasaccharide Derivatives of Neomycin B

  摘要：

  The clinically important antibiotic neomycin B was modified at position C5" by adding one extra sugar ring in the beta-configuration, and the observed pseudo-pentasaccharides were tested against various bacterial strains, including pathogenic and resistant strains. The designed antibiotics show antibacterial activity superior to that of neomycin B against pathogenic and resistant bacterial strains.

  DOI：

  10.1021/ol035213i

文献信息

• Bifunctional antibiotics for targeting rRNA and resistance-causing enzymes
  申请人：Baasov Timor

  公开号：US20050004052A1

  公开（公告）日：2005-01-06

  A novel group of aminoglycosides which share some structural features of currently available aminoglycosides with regard to the backbone, while also having significant structural differences. The similarity enables these aminoglycosides to be highly potent and effective antibiotics, while the significant differences enable these aminoglycosides to reduce or even block antibiotic resistance.

  一种新型氨基糖苷类药物，与目前已有的氨基糖苷类药物在骨架方面具有一些结构特征，同时又具有显著的结构差异。这种相似性使得这些氨基糖苷类药物具有很高的抗菌作用和有效性，而显著的差异使得这些氨基糖苷类药物能够减少甚至阻止抗生素耐药性的发展。
• Conjugated antimicrobial agents
  申请人：Technion Research & Development Foundation Limited

  公开号：US09149536B2

  公开（公告）日：2015-10-06

  Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via “click” chemistry.

  本文提供了两种抗生素的抗菌结合物，展现出对抗耐药细菌的改善活性，相比单独使用每种抗生素或它们的混合物，并且基本上没有产生抗性，以及制备这些结合物的过程、含有这些结合物的组合物，以及在医疗治疗中对抗病原微生物的用途。所披露的抗菌结合物由氨基糖苷类和非核糖体活性抗生素组成。其中一些抗菌结合物是通过“click”化学方法制备的。
• Branched aminoglycosides: Biochemical studies and antibacterial activity of neomycin B derivatives
  作者：Mariana Hainrichson、Varvara Pokrovskaya、Dalia Shallom-Shezifi、Micha Fridman、Valery Belakhov、Dina Shachar、Sima Yaron、Timor Baasov

  DOI：10.1016/j.bmc.2005.05.058

  日期：2005.10

  The C5"-OH group in neomycin B was glycosylated with a variety of mono- and di-saccharides to probe the effect of introduction of additional binding elements on antibacterial activity and interaction with the aminoglycosides modifying enzyme APH(3')-IIIa. The designed structures show antibacterial activity superior to that of neomycin B against pathogenic and resistant strains, while in parallel they demonstrate poor substrate activity with APH(3')IIIa. (c) 2005 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Evaluation of Novel Fluoroquinolone−Aminoglycoside Hybrid Antibiotics
  作者：Varvara Pokrovskaya、Valery Belakhov、Mariana Hainrichson、Sima Yaron、Timor Baasov

  DOI：10.1021/jm900028n

  日期：2009.4.23

  A series of new hybrid structures containing fluoroquinolone (ciprofloxacin) and aminoglycoside (neomycin) antibiotics linked via 1,2,3-triazole moiety were designed and synthesized, and their antibacterial activities were determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The nature of spacers in both the ciprofloxacin and neomycin parts greatly influenced the antibacterial activity. The majority of hybrids was significantly more potent than the parent neomycin and overcame most prevalent types of resistance associated with aminoglycosides. Selected hybrids inhibited bacterial protein synthesis with the potencies similar to or better than that of neomycin and were up to 32-fold more potent inhibitors than ciprofloxacin for the fluoroquinolone targets, DNA gyrase and toposiomerase IV, indicating a balanced dual mode of action. Significant delay of resistance formation was observed in both E. coli and B. subtilis to the treatment with ciprofloxacin-neomycin hybrid in comparison to that of each drug separately or their 1: 1 mixture.