3-O-descladinosyl-3-O-propargyl-6-O-methylerythromycin A 9-(E)-O-(1-isopropoxycyclohexyl)oxime | 1360059-90-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-O-descladinosyl-3-O-propargyl-6-O-methylerythromycin A 9-(E)-O-(1-isopropoxycyclohexyl)oxime
• 英文别名: (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-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-10-(1-propan-2-yloxycyclohexyl)oxyimino-4-prop-2-ynoxy-oxacyclotetradecan-2-one
• CAS: 1360059-90-0
• 化学式: C₄₂H₇₄N₂O₁₁
• 分子量: 783.056
• InChiKey: SPPGOPDXZHGIPP-QXQPDTFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  55
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  158
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  3-O-descladinosyl-3-O-propargyl-6-O-methylerythromycin A 9-(E)-O-(1-isopropoxycyclohexyl)oxime 在 盐酸 、 氨 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以100%的产率得到(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-12,13-dihydroxy-10-hydroxyimino-7-methoxy-3,5,7,9,11,13-hexamethyl-4-prop-2-ynoxy-oxacyclotetradecan-2-one
  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：

  5-O-desosaminyl-6-O-methylerythronolide A 9-oxime 在 potassium tert-butylate 、 吡啶盐酸盐 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.67h， 生成 3-O-descladinosyl-3-O-propargyl-6-O-methylerythromycin A 9-(E)-O-(1-isopropoxycyclohexyl)oxime
  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

• 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.