[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,6S,7S,8R,9R,11R,12E,13S,14R)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,16-dioxo-6-prop-2-enoxy-12-[(2,4,6-trimethylphenyl)methoxyimino]-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate | 1360059-88-6

• 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,6S,7S,8R,9R,11R,12E,13S,14R)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,16-dioxo-6-prop-2-enoxy-12-[(2,4,6-trimethylphenyl)methoxyimino]-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate
• CAS: 1360059-88-6
• 化学式: C₄₆H₇₂N₂O₁₂
• 分子量: 845.084
• InChiKey: ZPRJQNFXZHDNBD-GWHJRTRHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  60
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  150
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  5-溴嘧啶 、 [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,6S,7S,8R,9R,11R,12E,13S,14R)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,16-dioxo-6-prop-2-enoxy-12-[(2,4,6-trimethylphenyl)methoxyimino]-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate 在 trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) 、 四丁基溴化铵 、 sodium acetate 、 甲醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 75.0h， 以19%的产率得到3-O-descladinosyl-3-O-[3-(5-pyrimidyl)-(E)-prop-2-enyl]-6-O-methylerythromycin A 9-(E)-O-(2,4,6-trimethylbenzyl)oxime 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：

  3-O-descladinosyl-3-O-allyl-6-O-methylerythromycin A 9-(E)-oxime 在 吡啶 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.25h， 生成 [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(1R,2R,5R,6S,7S,8R,9R,11R,12E,13S,14R)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,16-dioxo-6-prop-2-enoxy-12-[(2,4,6-trimethylphenyl)methoxyimino]-3,15,17-trioxabicyclo[12.3.0]heptadecan-8-yl]oxy]-6-methyloxan-3-yl] acetate
  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