[(2S,3R,4S,6R)-2-[[(1R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-7-[(2R,4R,5S,6S)-5-benzoyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3-ethyl-10-methoxy-6,8,10,12,15,15,17-heptamethyl-2-methylidene-5-oxo-4,14,16-trioxabicyclo[11.3.1]heptadecan-9-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] benzoate | 484670-62-4

• 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-[[(1R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-7-[(2R,4R,5S,6S)-5-benzoyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3-ethyl-10-methoxy-6,8,10,12,15,15,17-heptamethyl-2-methylidene-5-oxo-4,14,16-trioxabicyclo[11.3.1]heptadecan-9-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] benzoate
• CAS: 484670-62-4
• 化学式: C₅₅H₈₁NO₁₄
• 分子量: 980.246
• InChiKey: WJEPTOXVQQJPAW-XDEWOITPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  70
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  156
• 氢给体数：
  0
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  [(2S,3R,4S,6R)-2-[[(1R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-7-[(2R,4R,5S,6S)-5-benzoyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3-ethyl-10-methoxy-6,8,10,12,15,15,17-heptamethyl-2-methylidene-5-oxo-4,14,16-trioxabicyclo[11.3.1]heptadecan-9-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] benzoate 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 N-氯代丁二酰亚胺 、 四氧化锇 、 二甲基硫 、 4-甲基苯磺酸吡啶 、 双(三甲基硅烷基)氨基钾 、 戴斯-马丁氧化剂 、 N-甲基吗啉氧化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 133.0h， 生成 [(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,5R,6R,7R,9R,11E,13S,14R)-13-ethenyl-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11-pentamethyl-2,4,10-trioxo-1-oxacyclotetradec-11-en-6-yl]oxy]-6-methyloxan-3-yl] benzoate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel C₁₂ Vinyl Ketolides

  摘要：

  A novel series Of C-12 vinyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens. The C-12 modification involves replacing the natural C-12 methyl group in the erythromycin core with a vinyl group via chemical synthesis. From the C-12 vinyl macrolide core, a series Of C-12 vinyl ketolides was prepared. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria. The C-12 vinyl ketolides 6j and 6k showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. However, the pharmacokinetic profiles Of C-12 vinyl ketolides 6j and 6k in rats differ from that of telithromycin by having higher lung-to-plasma ratios, larger volumes of distribution, and longer half-lives. These pharmacokinetic differences have a pharmacodynamic effect as both 6j and 6k exhibited better in vivo efficacy than telithromycin in rat lung infection models against Streptococcus pneumoniae and Haemophilus influenzae.

  DOI：

  10.1021/jm051157a
• 作为产物：
  描述：

  克拉霉素 在 2-二甲氨基嘧啶 、 sodium tetrahydroborate 、 氯化亚砜 、 4-甲基苯磺酸吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 32.0h， 生成 [(2S,3R,4S,6R)-2-[[(1R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-7-[(2R,4R,5S,6S)-5-benzoyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3-ethyl-10-methoxy-6,8,10,12,15,15,17-heptamethyl-2-methylidene-5-oxo-4,14,16-trioxabicyclo[11.3.1]heptadecan-9-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] benzoate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel C₁₂ Vinyl Ketolides

  摘要：

  A novel series Of C-12 vinyl erythromycin derivatives have been discovered which exhibit in vitro and in vivo potency against key respiratory pathogens. The C-12 modification involves replacing the natural C-12 methyl group in the erythromycin core with a vinyl group via chemical synthesis. From the C-12 vinyl macrolide core, a series Of C-12 vinyl ketolides was prepared. Several compounds were found to be potent against macrolide-sensitive and -resistant bacteria. The C-12 vinyl ketolides 6j and 6k showed a similar antimicrobial spectrum and comparable activity to the commercial ketolide telithromycin. However, the pharmacokinetic profiles Of C-12 vinyl ketolides 6j and 6k in rats differ from that of telithromycin by having higher lung-to-plasma ratios, larger volumes of distribution, and longer half-lives. These pharmacokinetic differences have a pharmacodynamic effect as both 6j and 6k exhibited better in vivo efficacy than telithromycin in rat lung infection models against Streptococcus pneumoniae and Haemophilus influenzae.

  DOI：

  10.1021/jm051157a

文献信息

• [EN] PYRIDYL SUBSTITUTED KETOLIDE ANTIBIOTICS<br/>[FR] ANTIBIOTIQUES A BASE DE KETOLIDE A SUBSTITUTION PYRIDYLE
  申请人：CHIRON CORP

  公开号：WO2004096822A3

  公开（公告）日：2004-12-16
• Synthesis and antibacterial activity of C12 des-methyl ketolides
  作者：Xiaodong Lin、Alice C. Rico、Daniel T. Chu、Georgia L. Carroll、Lynn Barker、Ribhi Shawar、Manoj C. Desai、Jacob J. Plattner

  DOI：10.1016/j.bmcl.2006.05.104

  日期：2006.9

  Synthesis of C-12 des-methyl ketolide is developed featuring an intramolecular epoxide formation/elimination process to establish the C-12 stereocenter. These ketolides are potent against several key respiratory pathogens, including erythromycin resistant erm- and mef-containing strains of Streptococcus pneumoniae. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and antibacterial activity of C-12 pyrazolinyl spiro ketolides
  作者：Lei Hu、Ping Lan、Qiu-Ling Song、Zhi-Jian Huang、Ping-Hua Sun、Chao Zhuo、Ying Wang、Shunian Xiao、Wei-Min Chen

  DOI：10.1016/j.ejmech.2010.09.060

  日期：2010.12

  A series of C-12 pyrazolinyl Spiro ketolide derivatives were designed and synthesized. The C-12 modifications involved replacing the natural C-12 methyl group in clarithromycin core with different pyrazolinyl spiros via chemical synthesis. Potential anti-bacterial activities against both erythromycin-susceptible and erythromycin-resistant bacteria were reported. (C) 2010 Elsevier Masson SAS. All rights reserved.