4-[[(2R,3S,4R,5S)-3-[(2R,3R,4R,5S,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2R,3R,4R,5S,6R)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxyoxolan-2-yl]methylamino]-4-oxobutanoic acid | 1092548-12-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[[(2R,3S,4R,5S)-3-[(2R,3R,4R,5S,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2R,3R,4R,5S,6R)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxyoxolan-2-yl]methylamino]-4-oxobutanoic acid
• CAS: 1092548-12-3
• 化学式: C₂₇H₅₁N₇O₁₅
• 分子量: 713.74
• InChiKey: WJWVQAQFPPLJOW-XTTLNOQSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -11.8
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  399
• 氢给体数：
  14
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  4-[[(2R,3S,4R,5S)-3-[(2R,3R,4R,5S,6S)-4,5-dihydroxy-3-(phenylmethoxycarbonylamino)-6-(phenylmethoxycarbonylaminomethyl)oxan-2-yl]oxy-5-[(1R,2R,3S,5R,6S)-2-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-3-(phenylmethoxycarbonylamino)-6-(phenylmethoxycarbonylaminomethyl)oxan-2-yl]oxy-6-hydroxy-3,5-bis(phenylmethoxycarbonylamino)cyclohexyl]oxy-4-hydroxyoxolan-2-yl]methylamino]-4-oxobutanoic acid 在 Pd(OH)2/C 、 氢气 作用下， 以 甲醇 、 水 、 溶剂黄146 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 10.0h， 生成 4-[[(2R,3S,4R,5S)-3-[(2R,3R,4R,5S,6S)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2R,3R,4R,5S,6R)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxyoxolan-2-yl]methylamino]-4-oxobutanoic acid
  参考文献：
  名称：

  Surprising Alteration of Antibacterial Activity of 5′′-Modified Neomycin against Resistant Bacteria

  摘要：

  A facile synthetic protocol for the production of neomycin B derivatives with various modifications at the 5 '' position has been developed. The structural activity relationship (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AMEs) was investigated. Enzymatic and molecular modeling studies reveal that the superb substrate promiscuity of AMEs allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivatives show enhanced antibacterial activity compared to the parent neomycin. Surprisingly, when testing synthetic neomycin derivatives against other human pathogens, two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert a high level of resistance against clinically used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that. new biological and antimicrobial activities can be obtained by chemical modifications of old drugs.

  DOI：

  10.1021/jm800997s

文献信息

• Rapid solid-phase syntheses of a peptidic-aminoglycoside library
  作者：Casey Kukielski、Krishnagopal Maiti、Sayantan Bhaduri、Sandra Story、Dev P. Arya

  DOI：10.1016/j.tet.2018.07.012

  日期：2018.8

  kanamycin and neomycin as the model aminoglycosides, was systematically and rapidly synthesized via solid phase peptide synthesis. Aminoglycosides were first converted into N-Boc protected carboxylic acids and fifteen l-amino acids were then used in the diversification of the full library. The approach outlined describes a rapid synthetic procedure where >200 PA compounds can be synthesized in a few months

  通过卡那霉素和新霉素作为模型氨基糖苷，通过固相肽合成系统地快速合成了单氨基酸和二氨基酸肽基氨基糖苷（PAs）文库。氨基糖苷类首先转化成Ñ -Boc保护的羧酸十五升然后，将α-氨基酸用于整个文库的多样化。概述的方法描述了一种快速合成方法，其中可以在几个月内合成纯度超过85-95％的200多种PA化合物。紫外线热变性评估了PA对模型人和细菌A位rRNA序列的结合稳定性。在PA之间的热熔解曲线中发现了显着差异，这归因于特定的氨基酸序列。新霉素功率放大器导致A位rRNA序列的稳定化大得多的变化（ΔT米 相比，卡那霉素的PA = 2.6-17.1℃）（=的ΔTm0.4-4.3℃）。卡那霉素PA对革兰氏阴性和革兰氏阳性细菌几乎没有活性，而新霉素PA具有显着的抗菌活性，MIC为2至16μM。