(2S,3R,4S,6R)-2-(((3R,4S,5S,6R,7R,9R,11S,12R,13S,14R,E)-10-(acetoxyimino)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecan-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate | 561327-05-7

• 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)-2-(((3R,4S,5S,6R,7R,9R,11S,12R,13S,14R,E)-10-(acetoxyimino)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecan-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate
• CAS: 561327-05-7
• 化学式: C₃₄H₆₀N₂O₁₂
• 分子量: 688.857
• InChiKey: WYSBTCUCJLONIG-BNMXKZFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  48.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  182.88
• 氢给体数：
  3.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,6R)-2-(((3R,4S,5S,6R,7R,9R,11S,12R,13S,14R,E)-10-(acetoxyimino)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecan-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate 在 吡啶 、 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 N-氯代丁二酰亚胺 、 copper(l) iodide 、 二甲基硫 、 potassium tert-butylate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.17h， 生成 (1R,2R,5R,7R,8R,9R,11R,12E,13S,14R)-12-[3-(5-benzoylthiophen-2-yl)prop-2-ynoxyimino]-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-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：

  E-2',4"-O-bis(trimethylsilyl)erythromycin A 9-O-(1-isopropyloxycyclohexyl)oxime 在 盐酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 (2S,3R,4S,6R)-2-(((3R,4S,5S,6R,7R,9R,11S,12R,13S,14R,E)-10-(acetoxyimino)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecan-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate
  参考文献：
  名称：

  醚连接烷基化物的设计和构效关系：3-O-descladinosyl 大环内酯和喹诺酮基序的杂化物

  摘要：

  TE-802 等酮内酯（3-酮）和 TEA0929 等酰基（3--酰基）对含有红霉素核糖体甲基化 () 基因的组成型抗性病原体无效。继我们之前对烷基化物（3--烷基）的研究之后，我们探索了将 (R/S) 3-descladinosyl erythromycin 与 6/7-quinolone 基序相结合的杂化物的构效关系，该杂化物具有扩展的醚连接间隔基，重点是其对具有组成型基因抗性的病原体的功效。优化的化合物不仅恢复了对诱导抗性病原体的功效，而且还表现出显着增强的对 和 的组成型抗性菌株的活性，这些菌株通常对现有的 C-3 修饰大环内酯类耐药。值得注意的是，hybrid（编码为 ZN-51）代表了一类开创性的药物，以其双重作用模式而著称，以核糖体为主要目标，拓扑异构酶为次要目标。作为大环内酯-喹诺酮杂合体的新型化学型，烷基化物是我们对抗大环内酯耐药细菌的宝贵补充。

  DOI：

  10.1016/j.bioorg.2024.107712

文献信息

• Synthesis and antibacterial activity of novel modified 5-O-mycaminose 14-membered ketolides
  作者：Yanpeng Xu、Xiaozhuo Chen、Di Zhu、Yi Liu、Zhehui Zhao、Longlong Jin、Chao Liu、Pingsheng Lei

  DOI：10.1016/j.ejmech.2013.08.023

  日期：2013.11

  A practicable method of introducing a side chain to the C-4' position of 5-O-desosamine in the 14membered ketolides was developed. And using this method, a series of novel modified 5-O-mycaminose ketolides were synthesized. These ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in vitro antibacterial activities against some respiratory pathogens. 15b and 18e showed comparable activity to telithromycin and clarithromycin. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and Antibacterial Activity of a Novel Series of Acylides:  3-<i>O</i>-(3-Pyridyl)acetylerythromycin A Derivatives
  作者：Tetsuya Tanikawa、Toshifumi Asaka、Masato Kashimura、Keiko Suzuki、Hiroyuki Sugiyama、Masakazu Sato、Kazuya Kameo、Shigeo Morimoto、Atsushi Nishida

  DOI：10.1021/jm020568d

  日期：2003.6.1

  A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLSB)-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-Dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.