[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,7R,8R,9R,11R,12E,13S,14R)-2-ethyl-12-[3-(1H-indol-5-yl)prop-2-ynoxyimino]-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6,16-trioxo-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate | 1429398-16-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,7R,8R,9R,11R,12E,13S,14R)-2-ethyl-12-[3-(1H-indol-5-yl)prop-2-ynoxyimino]-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6,16-trioxo-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate
• CAS: 1429398-16-2
• 化学式: C₄₄H₆₁N₃O₁₂
• 分子量: 823.981
• InChiKey: YPRPPYOGCPFPEW-WEJZWISJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  59
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  174
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,7R,8R,9R,11R,12E,13S,14R)-2-ethyl-12-[3-(1H-indol-5-yl)prop-2-ynoxyimino]-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6,16-trioxo-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate 在 甲醇 作用下， 反应 3.0h， 以40.3%的产率得到(1R,2R,5R,7R,8R,9R,11R,12E,13S,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-12-[3-(1H-indol-5-yl)prop-2-ynoxyimino]-9-methoxy-1,5,7,9,11,13-hexamethyl-3,15,17-trioxabicyclo[12.3.0]heptadecane-4,6,16-trione
  参考文献：
  名称：

  Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11,12-cyclic carbonate ketolides

  摘要：

  A series of 9-O-(3-aryl-2-propargyl)oxime ketolides 8 was synthesized and evaluated for in vitro antibacterial activity. Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLSB-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin. Especially, 8i (Ar=4-isoquinolyl) possessed an MIC of 0.064 mu g/mL against constitutively MLSB-resistant Streptococcus pneumoniae, and MICs of 0.032-0.064 mu g/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis. The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers. A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.054
• 作为产物：
  描述：

  [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,6S,7S,8R,9R,11R,12E,13S,14R)-2-ethyl-6-hydroxy-9-methoxy-1,5,7,9,11,13-hexamethyl-4,16-dioxo-12-prop-2-ynoxyimino-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate 在 bis-triphenylphosphine-palladium(II) chloride 、 N-氯代丁二酰亚胺 、 copper(l) iodide 、 二甲基硫 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 4.0h， 生成 [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,7R,8R,9R,11R,12E,13S,14R)-2-ethyl-12-[3-(1H-indol-5-yl)prop-2-ynoxyimino]-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6,16-trioxo-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate
  参考文献：
  名称：

  Synthesis, antibacterial activity and docking of 14-membered 9-O-(3-arylalkyl) oxime 11,12-cyclic carbonate ketolides

  摘要：

  A series of 9-O-(3-aryl-2-propargyl)oxime ketolides 8 was synthesized and evaluated for in vitro antibacterial activity. Among 8, 8b-8d, and 8h-8l displayed dramatically improved potency against inducibly MLSB-resistant and efflux-resistant pathogens as compared to clarithromycin and azithromycin. Especially, 8i (Ar=4-isoquinolyl) possessed an MIC of 0.064 mu g/mL against constitutively MLSB-resistant Streptococcus pneumoniae, and MICs of 0.032-0.064 mu g/mL against methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus hominis. The analog 10 with a propyl linker was less effective than both the corresponding 8 and 9 containing propynyl and propenyl linkers. A docking study was performed to gain insight into the binding mode of series 8 and 9 and to rationalize the disparity found in the SAR of 8 and 9. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.054