4''-O-(3-prop-2-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A | 936624-82-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4''-O-(3-prop-2-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
• 英文别名: 4"-O-(3-prop-2-ynyloxy-propyl)-azithromycin；(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-3,4,10-trihydroxy-13-[(2R,4R,5S,6S)-4-methoxy-4,6-dimethyl-5-(3-prop-2-ynoxypropoxy)oxan-2-yl]oxy-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one
• CAS: 936624-82-7
• 化学式: C₄₄H₈₀N₂O₁₃
• 分子量: 845.125
• InChiKey: AQNGLMKPARVHSG-QJKUXGJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  59
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  1-cyclopropyl-1,4-dihydro-6-iodo-4-oxo-3-quinolinecarboxylic acid 、 4''-O-(3-prop-2-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 7.0h， 生成 4''-O-{3-[3-(3-carboxy-1-cyclopropyl-4-oxo-1,4-dihydro-quinolin-6-yl)-prop-2-ynyloxy]-propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  WO2007/54296

  摘要：

  公开号：
• 作为产物：
  描述：

  2'-O-acetyl-4"-O-(3-prop-2-ynyloxy-propyl)-azithromycin-11,12-cyclic carbonate 在 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 生成 4''-O-(3-prop-2-ynyloxy-propyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A
  参考文献：
  名称：

  WO2007/54296

  摘要：

  公开号：

文献信息

• MACROLONES
  申请人：Alihodzic Sulejman

  公开号：US20090170791A1

  公开（公告）日：2009-07-02

  A compound of formula (I) or a pharmaceutically acceptable derivative thereof, having antimicrobial activity, processes for their preparation, compositions containing them and to their use in medicine.

  具有抗微生物活性的化合物式（I）或其药学上可接受的衍生物，制备它们的方法，包含它们的组合物以及它们在医学上的使用。
• WO2007/54296
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and properties of macrolones characterized by two ether bonds in the linker
  作者：Ivana Palej Jakopović、Goran Kragol、Andrew K. Forrest、Catherine S.V. Frydrych、Vlado Štimac、Samra Kapić、Maja Matanović Škugor、Marina Ilijaš、Hana Čipčić Paljetak、Dubravko Jelić、David J. Holmes、Deirdre M.B. Hickey、Donatella Verbanac、Vesna Eraković Haber、Sulejman Alihodžić

  DOI：10.1016/j.bmc.2010.07.007

  日期：2010.9

  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.