(2R,3S,4R,5S,6S,9R,10R,11S,12S,13R)-9,11-(S)-(ethylidenedioxy)-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide | 156629-09-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (2R,3S,4R,5S,6S,9R,10R,11S,12S,13R)-9,11-(S)-(ethylidenedioxy)-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide
• 英文别名: (1R,4S,5S,9S,10R,13R,14S,15S,17S,19R,20R)-4,7,7,10,13,14,17,19,20-nonamethyl-6,8,12,16,18-pentaoxatricyclo[13.3.1.15,9]icosane-2,11-dione
• CAS: 156629-09-3
• 化学式: C₂₄H₄₀O₇
• 分子量: 440.577
• InChiKey: JEINERCKSJSCAR-MHEDWNMCSA-N

物化性质

• 沸点：
  549.6±50.0 °C(predicted)
• 密度：
  0.993±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  31.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  80.29
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5S,6S,9R,10R,11S,12S,13R)-9,11-(S)-(ethylidenedioxy)-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide 在 samarium diiodide 、 二碘甲烷 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以79%的产率得到(2R,3S,4R,5S,6S,10R,11S,12S,13R)-11-hydroxy-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide
  参考文献：
  名称：

  Studies in Macrolide Synthesis: A Stereocontrolled Synthesis of Oleandolide Employing Reagent- and Substrate-Controlled Aldol Reactions of (S)-1-(Benzyloxy)-2-methylpentan-3-one

  摘要：

  A highly stereocontrolled total synthesis of oleandolide (2), the aglycon of the macrolide antibiotic oleandomycin (1), has been completed in 8% overall yield (20 steps longest Linear sequence, 26 steps in total) with 90% overall diastereoselectivity. Initially, reagent-controlled syn aldol reactions of (S)-1-(benzyloxy)-2-methylpentan-3-one ((S)-8) were employed to prepare adducts 6 (SS) and 7 (SA), which were elaborated to provide the two advanced fragments 33 and 27, respectively. Coupling of these fragments followed by functional group manipulation and macrolactonization gave the macrocyclic ketone 42, possessing S configuration at C-9. Elaboration of 42 to oleandolide, however, proved troublesome. Substrate-controlled syn and anti aldol reactions of ketone (S)-8, meanwhile, provided the adducts 6 (SS) and 7 (AA), which enabled synthesis, via fragments 64 and 60, of the key macrocyclic ketone intermediate 69, having R configuration at C-9. Stereoselective epoxidation of ketone 69, by reaction with dimethylsulfonium methylide under macrocyclic stereocontrol, provided the (8R)-epoxide 83; subsequent elaboration then gave oleandolide (2).

  DOI：

  10.1021/ja00104a010
• 作为产物：
  描述：

  (2S,3R,4S,5R,6R)-O-benzyl-3,5-(isopropylidenedioxy)-2,4,6-trimethyl-7-(phenylthio)heptan-1-ol 在 palladium on activated charcoal 、 镍 4-二甲氨基吡啶 、 sodium periodate 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 草酰氯 、 lithium diethylamide 、 sodium perchlorate 、 氢气 、 镍 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 、 叔丁醇 为溶剂， 反应 51.0h， 生成 (2R,3S,4R,5S,6S,9R,10R,11S,12S,13R)-9,11-(S)-(ethylidenedioxy)-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide
  参考文献：
  名称：

  Studies in Macrolide Synthesis: A Stereocontrolled Synthesis of Oleandolide Employing Reagent- and Substrate-Controlled Aldol Reactions of (S)-1-(Benzyloxy)-2-methylpentan-3-one

  摘要：

  A highly stereocontrolled total synthesis of oleandolide (2), the aglycon of the macrolide antibiotic oleandomycin (1), has been completed in 8% overall yield (20 steps longest Linear sequence, 26 steps in total) with 90% overall diastereoselectivity. Initially, reagent-controlled syn aldol reactions of (S)-1-(benzyloxy)-2-methylpentan-3-one ((S)-8) were employed to prepare adducts 6 (SS) and 7 (SA), which were elaborated to provide the two advanced fragments 33 and 27, respectively. Coupling of these fragments followed by functional group manipulation and macrolactonization gave the macrocyclic ketone 42, possessing S configuration at C-9. Elaboration of 42 to oleandolide, however, proved troublesome. Substrate-controlled syn and anti aldol reactions of ketone (S)-8, meanwhile, provided the adducts 6 (SS) and 7 (AA), which enabled synthesis, via fragments 64 and 60, of the key macrocyclic ketone intermediate 69, having R configuration at C-9. Stereoselective epoxidation of ketone 69, by reaction with dimethylsulfonium methylide under macrocyclic stereocontrol, provided the (8R)-epoxide 83; subsequent elaboration then gave oleandolide (2).

  DOI：

  10.1021/ja00104a010

文献信息

• Substrate-Controlled Aldol Reactions of Chiral Ethyl Ketones: Application to the Total Synthesis of Oleandomycin
  作者：Ian Paterson、Richard A. Ward、Pedro Romea、Roger D. Norcross

  DOI：10.1021/ja00087a068

  日期：1994.4