4''-O-(3-pent-3-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A | 936624-94-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4''-O-(3-pent-3-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
• 英文别名: 4"-O-(3-pent-4-ynyloxy-propyl)azithromycin
• CAS: 936624-94-1
• 化学式: C₄₆H₈₄N₂O₁₃
• 分子量: 873.179
• InChiKey: BIMUCWRANLRICC-QIMVLXEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  61.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  178.31
• 氢给体数：
  4.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  1-ethyl-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 4''-O-(3-pent-3-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以42%的产率得到4''-O-{3-[5-(3-carboxy-1-ethyl-4-oxo-1,4-dihydro-quinolin-6-yl)-pent-4-ynyloxy]-propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Synthesis and properties of macrolones characterized by two ether bonds in the linker

  摘要：

  In this paper synthesis of macrolones 1-18 starting from azithromycin is reported. Two key steps in the construction of the linker between macrolide and quinolone moiety, are formation of central ether bond by alkylation of unactivated OH group, and formation of terminal C-C bond at 6-position of the quinolone unit. Due to the difficulty in formation of these two bonds the study of alternative synthetic methodologies and optimization of the conditions for the selected routes was required. Formation of C-4"-O-ether bond was completed by modified Michael addition, whereas O-alkylation via diazonium cation proved to be the most effective in formation of the central allylic or propargylic ether bond. Comparison of Heck and Sonogashira reaction revealed the former as preferred route to the C-C bond formation at C(6) position of the quinolone unit. Most of the target compounds exhibited highly favorable antibacterial activity against common respiratory pathogens, without significant cytotoxicity profile when tested in vitro on eukaryotic cell lines. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.007
• 作为产物：
  描述：

  4"-O-(3-aminopropyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A 、 4-戊炔-1-醇 在 甲酸 、 sodium nitrite 作用下， 以21%的产率得到4''-O-(3-pent-3-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  Synthesis and properties of macrolones characterized by two ether bonds in the linker

  摘要：

  In this paper synthesis of macrolones 1-18 starting from azithromycin is reported. Two key steps in the construction of the linker between macrolide and quinolone moiety, are formation of central ether bond by alkylation of unactivated OH group, and formation of terminal C-C bond at 6-position of the quinolone unit. Due to the difficulty in formation of these two bonds the study of alternative synthetic methodologies and optimization of the conditions for the selected routes was required. Formation of C-4"-O-ether bond was completed by modified Michael addition, whereas O-alkylation via diazonium cation proved to be the most effective in formation of the central allylic or propargylic ether bond. Comparison of Heck and Sonogashira reaction revealed the former as preferred route to the C-C bond formation at C(6) position of the quinolone unit. Most of the target compounds exhibited highly favorable antibacterial activity against common respiratory pathogens, without significant cytotoxicity profile when tested in vitro on eukaryotic cell lines. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.007

文献信息

• WO2007/54296
  申请人：——

  公开号：——

  公开（公告）日：——