methyl (E)-4-methyl-7-phenylmethoxyhept-4-enoate | 1254369-08-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (E)-4-methyl-7-phenylmethoxyhept-4-enoate
• CAS: 1254369-08-8
• 化学式: C₁₆H₂₂O₃
• 分子量: 262.349
• InChiKey: DURUHBKJRYYGAE-VGOFMYFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (E)-4-methyl-7-phenylmethoxyhept-4-enoate 在 咪唑 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 2,6-二甲基吡啶 、 甲醇 、 potassium osmate(VI) dihydrate 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 2,6-二叔丁基-4-甲基吡啶 、 草酰氯 、 甲基磺酰胺 、 cerium(III) chloride heptahydrate 、 三氟甲磺酸二丁硼 、 2,4,6-三氯苯甲酰氯 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 水 、 氢气 、 双氧水 、 silver trifluoromethanesulfonate 、 1,8-双二甲氨基萘 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 溶剂黄146 、 二甲基亚砜 、 氢化奎尼定 1,4-(2,3-二氮杂萘)二醚 、 三乙胺 、 lithium hydroxide 、 potassium hexacyanoferrate(III) 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 168.17h， 生成 C₄₈H₇₇N₅O₁₂Si
  参考文献：
  名称：

  Desmethyl Macrolides: Synthesis and Evaluation of 4,8,10-Tridesmethyl Telithromycin

  摘要：

  There is an urgent need to discover new drugs to address the pressing problem of antibiotic resistance. Macrolide antibiotics such as erythromycin (1) are safe, broad spectrum antibiotics used in the clinic since 1954. Herein, we report the synthesis and evaluation of 4,8,10-tridesmethyl telithromycin (3), a novel desmethyl analogue of the third-generation drug telithromycin (2), which is a semisynthetic derivative of 1. Analogue 3 was found to possess antibiotic activity and was superior to telithromycin (2) when tested against resistant strains of Staphylococcus aureus possessing an A -> T mutation at position 2058 (Escherichia coli numbering).

  DOI：

  10.1021/ml1002184
• 作为产物：
  描述：

  3-苄氧基丙醛 在 碘 、 magnesium 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 37.0h， 生成 methyl (E)-4-methyl-7-phenylmethoxyhept-4-enoate
  参考文献：
  名称：

  Desmethyl Macrolides: Synthesis and Evaluation of 4,8,10-Tridesmethyl Telithromycin

  摘要：

  There is an urgent need to discover new drugs to address the pressing problem of antibiotic resistance. Macrolide antibiotics such as erythromycin (1) are safe, broad spectrum antibiotics used in the clinic since 1954. Herein, we report the synthesis and evaluation of 4,8,10-tridesmethyl telithromycin (3), a novel desmethyl analogue of the third-generation drug telithromycin (2), which is a semisynthetic derivative of 1. Analogue 3 was found to possess antibiotic activity and was superior to telithromycin (2) when tested against resistant strains of Staphylococcus aureus possessing an A -> T mutation at position 2058 (Escherichia coli numbering).

  DOI：

  10.1021/ml1002184

文献信息

• Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin
  作者：Venkata Velvadapu、Ian Glassford、Miseon Lee、Tapas Paul、Charles DeBrosse、Dorota Klepacki、Meagan C. Small、Alexander D. MacKerell、Rodrigo B. Andrade

  DOI：10.1021/ml200254h

  日期：2012.3.8

  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.