(2S,3R,4S,6R)-2-(((3R,4S,6R,7R,9R,13S,14R,E)-4-((tert-butyldimethylsilyl)oxy)-14-ethyl-13-hydroxy-7-methoxy-3,7,9,13-tetramethyl-2,10-dioxooxacyclotetradec-11-en-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl methyl carbonate | 1355616-44-2

• 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-(((3R,4S,6R,7R,9R,13S,14R,E)-4-((tert-butyldimethylsilyl)oxy)-14-ethyl-13-hydroxy-7-methoxy-3,7,9,13-tetramethyl-2,10-dioxooxacyclotetradec-11-en-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl methyl carbonate
• CAS: 1355616-44-2
• 化学式: C₃₆H₆₅NO₁₁Si
• 分子量: 715.998
• InChiKey: WGUOAAHELFMXLZ-CWNZSPCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  49.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  139.29
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,6R)-2-(((3R,4S,6R,7R,9R,13S,14R,E)-4-((tert-butyldimethylsilyl)oxy)-14-ethyl-13-hydroxy-7-methoxy-3,7,9,13-tetramethyl-2,10-dioxooxacyclotetradec-11-en-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl methyl carbonate 在 sodium hydride 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.5h， 生成
  参考文献：
  名称：

  Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin

  摘要：

  Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling, and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the third-generation drug telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity, suggesting that it plays an important role in antibiotic function.

  DOI：

  10.1021/ml200254h
• 作为产物：
  描述：

  (R)-5-((R)-3-(benzyloxy)-1-((triethylsilyl)oxy)propyl)-5-methyldihydrofuran-2(3H)-one 在 咪唑 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 2,6-二叔丁基-4-甲基吡啶 、 cerium(III) chloride 、 草酰氯 、 三氟甲磺酸二丁硼 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氢气 、 双氧水 、 silver trifluoromethanesulfonate 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 溶剂黄146 、 二甲基亚砜 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 lithium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 149.5h， 生成 (2S,3R,4S,6R)-2-(((3R,4S,6R,7R,9R,13S,14R,E)-4-((tert-butyldimethylsilyl)oxy)-14-ethyl-13-hydroxy-7-methoxy-3,7,9,13-tetramethyl-2,10-dioxooxacyclotetradec-11-en-6-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl methyl carbonate
  参考文献：
  名称：

  Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin

  摘要：

  Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling, and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the third-generation drug telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity, suggesting that it plays an important role in antibiotic function.

  DOI：

  10.1021/ml200254h