erythromycin A 9-oxime benzyl ether

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: erythromycin A 9-oxime benzyl ether
• 英文别名: erythromycin A 9-(E)-O-benzyloxime；(3R,4S,5S,6R,7R,9R,10E,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-10-phenylmethoxyimino-oxacyclotetradecan-2-one
• 化学式: C₄₄H₇₄N₂O₁₃
• 分子量: 839.077
• InChiKey: XNQSMGCYXKVOGL-QJIYQREHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  59
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  198
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  erythromycin A 9-oxime benzyl ether 在 吡啶 、 盐酸 、 吡啶盐酸盐 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 4.17h， 生成 3-O-descladinosyl-2'-O-acetyl-6-O-methylerythromycin A 9-(E)-O-benzyloxime 11,12-cyclic carbonate
  参考文献：
  名称：

  Structure–activity relationships of novel alkylides: 3-O-Arylalkyl clarithromycin derivatives with improved antibacterial activities

  摘要：

  A series of novel alkylides, possessing 3-O-arylallcyl group instead of 3-O-cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2-propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z-prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLSB resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 mu g/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLSB resistant strains (MICs of 0.125-0.5 mu g/mL) resistant to clarithromycin and azithromycin (MICs of 1 >254 mu g/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.023
• 作为产物：
  描述：

  氯化苄 、 erythromycin A 9-(E)-oxime 在 potassium hydroxide 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以89.3%的产率得到erythromycin A 9-oxime benzyl ether
  参考文献：
  名称：

  Structure–activity relationships of novel alkylides: 3-O-Arylalkyl clarithromycin derivatives with improved antibacterial activities

  摘要：

  A series of novel alkylides, possessing 3-O-arylallcyl group instead of 3-O-cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2-propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z-prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLSB resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 mu g/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLSB resistant strains (MICs of 0.125-0.5 mu g/mL) resistant to clarithromycin and azithromycin (MICs of 1 >254 mu g/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.023

文献信息

• Chemistry and Biology of Macrolide Antiparasitic Agents
  作者：Younjoo Lee、Jun Yong Choi、Hong Fu、Colin Harvey、Sandeep Ravindran、William R. Roush、John C. Boothroyd、Chaitan Khosla

  DOI：10.1021/jm101593u

  日期：2011.4.28

  antibacterial agents inhibit parasite proliferation by targeting the apicoplast ribosome. Motivated by the long-term goal of identifying antiparasitic macrolides that lack antibacterial activity, we have systematically analyzed the structure−activity relationships among erythromycin analogues and have also investigated the mechanism of action of selected compounds. Two lead compounds, N-benzylazithromycin (11)

  大环内酯类抗菌剂通过靶向顶质体核糖体来抑制寄生虫增殖。出于确定缺乏抗菌活性的抗寄生虫大环内酯类的长期目标，我们系统地分析了红霉素类似物之间的构效关系，并研究了所选化合物的作用机制。两种先导化合物，N-苄基阿奇霉素 ( 11 ) 和N-苯丙基阿奇霉素( 30))，被鉴定为具有比红霉素或阿奇霉素显着更高的抗寄生虫活性和更低的抗菌活性。基于与细菌核糖体结合的阿奇霉素共晶结构的分子模型表明，由于与核糖体 L22 蛋白的物种特异性相互作用，去甲基阿奇霉素 N-9 位的取代基可以提高选择性。与其他大环内酯类化合物一样，这些先导化合物表现出强烈的“延迟死亡表型”；然而，它们对弓形虫复制的早期影响更为明显。
• WO2006/50943
  申请人：——

  公开号：——

  公开（公告）日：——
• Structure–activity relationships of novel alkylides: 3-O-Arylalkyl clarithromycin derivatives with improved antibacterial activities
  作者：Jian-Hua Liang、Xiao-Li Li、He Wang、Kun An、Yue-Ying Wang、Ying-Chun Xu、Guo-Wei Yao

  DOI：10.1016/j.ejmech.2012.01.023

  日期：2012.3

  A series of novel alkylides, possessing 3-O-arylallcyl group instead of 3-O-cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2-propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z-prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLSB resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 mu g/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLSB resistant strains (MICs of 0.125-0.5 mu g/mL) resistant to clarithromycin and azithromycin (MICs of 1 >254 mu g/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes. (C) 2012 Elsevier Masson SAS. All rights reserved.