3,2',6',3'',4'''-pentakis(N-tert-butoxucarbonyl)arbekacin | 189157-31-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3,2',6',3'',4'''-pentakis(N-tert-butoxucarbonyl)arbekacin
• CAS: 189157-31-1
• 化学式: C₄₇H₈₄N₆O₂₀
• 分子量: 1053.21
• InChiKey: BXZQOXFUDNSQGU-NKYYKNTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.43
• 重原子数：
  73.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  358.82
• 氢给体数：
  11.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  3,2',6',3'',4'''-pentakis(N-tert-butoxucarbonyl)arbekacin 在 palladium on activated charcoal 吡啶 、 甲醇 、 4-二甲氨基吡啶 、 sodium azide 、 氢气 、 sodium methylate 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-deoxy-5-epiamino-arbekacin
  参考文献：
  名称：

  Synthesis and antibacterial activity of 5-deoxy-5-episubstituted arbekacin derivatives

  摘要：

  5-Deoxy-5-episubstituted arbekacin derivatives have been designed and efficiently synthesized. The synthetic compounds showed potent antibacterial activity against both Staphylococcus aureus, including methicillin-resistant S. aureus, and Pseudomonas aeruginosa. In particular, these derivatives were superior to arbekacin against MRSA strains expressing the bifunctional aminoglycoside-modifying enzyme AAQ6')-APH(2"). The antibacterial activity of the 5-deoxy-5-episubstituted arbekacin derivatives against Pseudomonas aeruginosa was markedly influenced by the efflux system of MexXY/OprM. The 6'-N-methyl derivative of the 5-epi arbekacin was effective against Pseudomonas aeruginosa expressing the aminoglycoside-modifying enzyme AAC(6'). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.065
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 阿贝卡星 在 硫酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 以98%的产率得到3,2',6',3'',4'''-pentakis(N-tert-butoxucarbonyl)arbekacin
  参考文献：
  名称：

  Synthesis and antibacterial activity of 4″ or 6″-alkanoylamino derivatives of arbekacin

  摘要：

  阿贝卡星是一种氨基糖苷类抗生素，因对耐甲氧西林的金黄色葡萄球菌显示出强效而成为重要药物。然而，由于双功能氨基糖苷修饰酶导致的耐药性已被观察到，成为医学实践中的一大难题。为了研制对耐药菌有活性新型阿贝卡星衍生物，我们对阿贝卡星的3-氨基糖部分的C-4''位点和6''位点进行了修饰。通过对6''-位置的立体选择性胺化，得到了6''-氨基-6''-脱氧阿贝卡星（1），并将其转化为各种6''-N-烷酰基衍生物（6a-z）。此外，对4''-羟基的区域选择性修饰得到了4''-脱氧-4''-表氨基阿贝卡星（2）及其4''-N-烷酰基衍生物（12和13）。评估了这些化合物对金黄色葡萄球菌（包括耐阿贝卡星的菌株）的抗菌活性。观察到6''-氨基-6''-N-[（S）-4-氨基-2-羟基丁酰基]-6''-脱氧阿贝卡星（6o）显示出优异的抗菌活性，甚至优于阿贝卡星。

  DOI：

  10.1038/ja.2015.61

文献信息

• EP1710248
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of 2″-oxidized derivatives of 5-deoxy-5-epi-5-fluoro-dibekacin and -arbekacin, and study on structure-chemical shift relationships of urethane(or amide)-type NH protons in synthetic intermediates
  作者：Yoshihiko Kobayashi、Tsutomu Tsuchiya

  DOI：10.1016/s0008-6215(96)00318-7

  日期：1997.3

  Three 2''-modified dibekacin-analogs have been prepared as potential compounds active against resistant bacteria producing 2''-O-phosphotransferases; one is 5-deoxy-5,2''-diepi-5-fluorodibekacin (9) prepared from a suitably protected 2''-O-triflyl derivative through the 2'',3''-cyclic carbamate, and the others are 2''-oxo derivatives (12 and 22, both as the hydrate) of 5-deoxy-5-epi-5-fluoro-dibekacin and -arbekacin prepared through oxidation at C-2'' of suitably protected derivatives. Relationships between the t-butoxycarbonyl(= Boc)-NH-shifts of per-N-Boc synthetic intermediates and their structures were studied. It was found that the shifts, measured in pyridine-d(5) at 80 degrees C, which spread over a close range (delta 6-7 ppm), are sensitively influenced by nearby and surrounding groups around the BocNH group in respect of electron-withdrawing character, hydrogen bonding (BocNH ... acceptor), and also solvent effects (BocNH ... NC5H5). (C) 1997 Elsevier Science Ltd.
• Effect of varying the 4″-position of arbekacin derivatives on antibacterial activity against MRSA and Pseudomonas aeruginosa
  作者：Yukiko Hiraiwa、Nobuto Minowa、Takayuki Usui、Yoshihisa Akiyama、Kazunori Maebashi、Daishiro Ikeda

  DOI：10.1016/j.bmcl.2007.08.059

  日期：2007.11

  4 ''-Deoxy-4 ''-episubstituted arbekacin derivatives and 4 ''-epi-5-deoxy-5-episubstituted arbekacin derivatives were designed and synthesized. Arbekacin and 4 ''-epiarbekacin both displayed the same antibacterial activity against Staphylococcus aureus (including methicillin-resistant S. aureus (MRSA)) and Pseudomonas aeruginosa. The 4 ''-epi-5-deoxy-5-episubstituted arbekacin derivatives showed potent antibacterial activity. Among them, the antibacterial activity of 5,4 ''-diepiarbekacin was superior to that of arbekacin or 5-episubstituted arbekacin against Gram-positive and Gram-negative bacteria. The 6 '-N-methyl derivative of the 5,4 ''-diepiarbekacin was effective against P. aeruginosa expressing an aminoglycoside-modifying enzyme AAC(6 ')-Ib. (C) 2007 Elsevier Ltd. All rights reserved.