(2R,3S,4R,5S,6S,9R,10R,11R,12R,13R)-3,5,9,11-tetrahydroxy-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide | 119870-68-7

• 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,11R,12R,13R)-3,5,9,11-tetrahydroxy-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide
• CAS: 119870-68-7
• 化学式: C₂₀H₃₆O₆
• 分子量: 372.502
• InChiKey: ZLSQOQABGXDEJZ-DVSJIIGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26.0
• 可旋转键数：
  0.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  107.22
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5S,6S,9R,10R,11R,12R,13R)-3,5,9,11-tetrahydroxy-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide 在 aluminum oxide 、 camphor-10-sulfonic acid 、 碳酸氢钠 、 pyridinium chlorochromate 作用下， 以 甲苯 为溶剂， 反应 19.33h， 生成 (2R,3S,4R,5S,6S,8S,10R,11R,12R,13R)-3,5-<(p-bromobenzylidene)dioxy>-8,8-(epoxymethano)-11-hydroxy-2,4,6,10,12,13-hexamethyl-9-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：

  (2R,3R,4S,5S,6R)-2,4-(S)-(ethylidenedioxy)-6-<(p-methoxybenzyl)oxy>-3,5-dimethylheptanal 在 palladium on activated charcoal 、 镍 盐酸 、 4-二甲氨基吡啶 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 草酰氯 、 lithium diethylamide 、 sodium perchlorate 、 氢气 、 双(三甲基硅烷基)氨基钾 、 镍 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 、 叔丁醇 为溶剂， 反应 30.5h， 生成 (2R,3S,4R,5S,6S,9R,10R,11R,12R,13R)-3,5,9,11-tetrahydroxy-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide
  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

• Synthesis of oleandomycin through the intact aglycone, oleandolide
  作者：Kuniaki Tatsuta、Yoshiyuki Kobayashi、Hiroki Gunji、Hirokazu Masuda

  DOI：10.1016/s0040-4039(00)80397-4

  日期：——

  Oleandomycin has been reconstructed by an introduction of the two sugar units onto the intact aglycone, oleandolide, which was first synthesized through the stereoselective oxidation of the 8-exo-methylene derivative.

  通过将两个糖单元引入完整的糖苷配基油酸内酯中，重新构建了奥林霉素，该糖苷酸首先通过8-外-亚甲基衍生物的立体选择性氧化合成。
• Synthesis of macrolide antibiotics 21. Retrosynthetic analysis of oleandonolide and macrolactonization of its seco-acid
  作者：A. F. Sviridov、D. V. Yashunskii、A. S. Kuz'min、N. K. Kochetkov

  DOI：10.1007/bf00960424

  日期：1991.9

  A retrosynthetic scheme for preparing oleandonolide was examined, and the possibility of macrolactonization of the seco-acid of oleandonolide to a lactone was investigated.