[(3R,4S)-4-hydroxy-4-methylhex-5-en-3-yl] (2R,3S,5R,6R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-6-methoxy-2,6-dimethyl-5-triethylsilyloxynonanoate | 1254369-17-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: [(3R,4S)-4-hydroxy-4-methylhex-5-en-3-yl] (2R,3S,5R,6R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-6-methoxy-2,6-dimethyl-5-triethylsilyloxynonanoate
• CAS: 1254369-17-9
• 化学式: C₃₇H₇₈O₇Si₃
• 分子量: 719.279
• InChiKey: VKTZQATVSHCROQ-PZDGJZPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.26
• 重原子数：
  47
• 可旋转键数：
  25
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(3R,4S)-4-hydroxy-4-methylhex-5-en-3-yl] (2R,3S,5R,6R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-6-methoxy-2,6-dimethyl-5-triethylsilyloxynonanoate 在 咪唑 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 2,6-二甲基吡啶 、 甲醇 、 sodium tetrahydroborate 、 2,6-二叔丁基-4-甲基吡啶 、 cerium(III) chloride heptahydrate 、 四丁基氟化铵 、 silver trifluoromethanesulfonate 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 51.5h， 生成 [(2S,3R,4S,6R)-2-[[(3R,4S,6R,7R,10R,11E,13S,14R)-4-[tert-butyl(dimethyl)silyl]oxy-14-ethyl-10,13-dihydroxy-7-methoxy-3,7,13-trimethyl-2-oxo-1-oxacyclotetradec-11-en-6-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] methyl carbonate
  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：

  methyl (E)-4-methyl-7-phenylmethoxyhept-4-enoate 在 咪唑 、 2,6-二甲基吡啶 、 potassium osmate(VI) dihydrate 、 lithium aluminium tetrahydride 、 草酰氯 、 甲基磺酰胺 、 三氟甲磺酸二丁硼 、 2,4,6-三氯苯甲酰氯 、 palladium 10% on activated carbon 、 水 、 氢气 、 双氧水 、 1,8-双二甲氨基萘 、 potassium carbonate 、 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 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 72.17h， 生成 [(3R,4S)-4-hydroxy-4-methylhex-5-en-3-yl] (2R,3S,5R,6R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-6-methoxy-2,6-dimethyl-5-triethylsilyloxynonanoate
  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

• Total Synthesis of (−)-4,8,10-Tridesmethyl Telithromycin
  作者：Venkata Velvadapu、Tapas Paul、Bharat Wagh、Ian Glassford、Charles DeBrosse、Rodrigo B. Andrade

  DOI：10.1021/jo201319b

  日期：2011.9.16

  Novel sources of antibiotics are required to address the serious problem of antibiotic resistance. Telithromycin (2) is a third-generation macrolide antibiotic prepared from erythromycin (1) and used clinically since 2004. Herein we report the details of our efforts that ultimately led to the total synthesis of (-)-4,8,10-tridesmethyl telithromycin (3) wherein methyl groups have been replaced with hydrogens. The synthesis of desmethyl macrolides has emerged as a novel strategy for preparing bioactive antibiotics.