11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyranosyl)oxy]-6O-methyl-3-oxoerythromycin-2'-trimethylsilyloxy-2α-fluoro | 244307-84-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyranosyl)oxy]-6O-methyl-3-oxoerythromycin-2'-trimethylsilyloxy-2α-fluoro
• 英文别名: (3S,5R,6R,7R,9R,11E,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-trimethylsilyloxyoxan-2-yl]oxy-14-ethyl-3-fluoro-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradec-11-ene-2,4,10-trione
• CAS: 244307-84-4
• 化学式: C₃₃H₅₈FNO₉Si
• 分子量: 659.909
• InChiKey: LNZINMXBHYESBX-WBLAGACCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.62
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyranosyl)oxy]-6O-methyl-3-oxoerythromycin-2'-trimethylsilyloxy-2α-fluoro 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyrasonyl)oxy]-6O-methyl-3-oxoerythromycin-2'-acetoxy-2α-fluoro
  参考文献：
  名称：

  β-Keto-ester chemistry and ketolides. synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides

  摘要：

  The effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2. is beneficial with regard to the overall antibacterial spectrum whereas the enol-ether and 2,3 unsaturated compounds, as well as the bulky gem dimethyl or 2-chloro derivatives, are less active particularly against erythromycin resistant strains. A 2-fluoro ketolide derivative demonstrates good antibacterial activity and in vivo efficacy against multi-resistant Streptococcus pneumoniae. Compared to azithromycin against Haemophilus influenzae, this compound is equivalent in vitro and slightly more active in vivo. These results demonstrate that within the ketolide class, to retain good antibacterial activity, position needs to remain tetrahedral and tolerates only very small substituents such as fluorine. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00392-9
• 作为产物：
  描述：

  11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyranosyl)oxy]-6O-methyl-3-oxoerythromycin-2'-trimethylsilyloxy 在 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.75h， 生成 11-deoxy-10,11-didehydro-3-de[(2,6-dideoxy-3C-methyl-3O-methyl-α-L-ribohexopyranosyl)oxy]-6O-methyl-3-oxoerythromycin-2'-trimethylsilyloxy-2α-fluoro
  参考文献：
  名称：

  2-halogenated derivatives of 5-0 desosaminyl-erythronolide A, their preparation process and their antibiotic use

  摘要：

  该式中的新化合物具有抗生素性质，其中取代基的定义如申请中所述。

  公开号：

  US06352983B1

文献信息

• 2-halogenated derivatives of 5-0 desosaminyl-erythronolide A, their preparation process and their antibiotic use
  申请人：Aventis Pharma S.A.

  公开号：US06352983B1

  公开（公告）日：2002-03-05

  Novel compounds of the formula wherein the substituents are defined as in the application having antibiotic properties.

  该式中的新化合物具有抗生素性质，其中取代基的定义如申请中所述。
• β-Keto-ester chemistry and ketolides. synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides
  作者：Alexis Denis、François Bretin、Claude Fromentin、A Bonnet、Alain Bonnefoy、Constantin Agouridas、G Piltan

  DOI：10.1016/s0960-894x(00)00392-9

  日期：2000.9

  The effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2. is beneficial with regard to the overall antibacterial spectrum whereas the enol-ether and 2,3 unsaturated compounds, as well as the bulky gem dimethyl or 2-chloro derivatives, are less active particularly against erythromycin resistant strains. A 2-fluoro ketolide derivative demonstrates good antibacterial activity and in vivo efficacy against multi-resistant Streptococcus pneumoniae. Compared to azithromycin against Haemophilus influenzae, this compound is equivalent in vitro and slightly more active in vivo. These results demonstrate that within the ketolide class, to retain good antibacterial activity, position needs to remain tetrahedral and tolerates only very small substituents such as fluorine. (C) 2000 Elsevier Science Ltd. All rights reserved.