(2R,3S,4R,5S,6S,9S,10R,11S,12S,13R)-9,11-bis(tert-butyldimethylsiloxy)-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide | 141566-30-5

• 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,9S,10R,11S,12S,13R)-9,11-bis(tert-butyldimethylsiloxy)-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-oxotetradecanolide
• 英文别名: (1S,2R,5R,6S,7S,8R,9S,12S,13S,17R)-7,9-bis[[tert-butyl(dimethyl)silyl]oxy]-2,5,6,8,12,15,15,17-octamethyl-4,14,16-trioxabicyclo[11.3.1]heptadecane-3,10-dione
• CAS: 141566-30-5
• 化学式: C₃₄H₆₆O₇Si₂
• 分子量: 643.065
• InChiKey: QYGGNVBBSSQKRL-LHRQLGMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.37
• 重原子数：
  43.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  80.29
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  (2S,3S,4S,5R,6S)-7-hydroxy-3,5-(isopropylidenedioxy)-2,4,6-trimethylheptyl p-toluenesulfonate 在 palladium on activated charcoal 、 W-2 Ra Ni 4-二甲氨基吡啶 、 potassium permanganate 、 sodium periodate 、 草酰氯 、 氢气 、 二甲基亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 水 、 甲苯 、 叔丁醇 为溶剂， 反应 33.5h， 生成 (2R,3S,4R,5S,6S,9S,10R,11S,12S,13R)-9,11-bis(tert-butyldimethylsiloxy)-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 a (9S)-macrolide intermediate for oleandomycin using chiral boron reagents.

  摘要：

  The (9S)-macrolide 1 (P = TBS) was prepared in 14 steps (5% yield) with 63% overall ds starting from the ethyl ketone (S)-2. The C1-C7 and C8-C13 segments, 3 and 4, were obtained via boron enolate aldol reactions mediated by (+)- and (-)-(Ipc)2BOTf, respectively.

  DOI：

  10.1016/s0040-4039(00)91728-3

文献信息

• Studies in Macrolide Synthesis: A Stereocontrolled Synthesis of Oleandolide Employing Reagent- and Substrate-Controlled Aldol Reactions of (S)-1-(Benzyloxy)-2-methylpentan-3-one
  作者：Ian Paterson、Roger D. Norcross、Richard A. Ward、Pedro Romea、M. Anne Lister

  DOI：10.1021/ja00104a010

  日期：1994.12

  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).