(2R,3S,4R,5S,6S,9R,10R,11R,12R,13R)-9,11-dihydroxy-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide | 160691-43-0

• 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)-9,11-dihydroxy-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide
• 英文别名: (9R)-3,5-O-isopropylidene-8,8a-deoxa-9-dihydrooleandonolide；(1S,2R,5R,6R,7R,8R,9R,12S,13S,17R)-7,9-dihydroxy-2,5,6,8,12,15,15,17-octamethyl-10-methylidene-4,14,16-trioxabicyclo[11.3.1]heptadecan-3-one
• CAS: 160691-43-0
• 化学式: C₂₃H₄₀O₆
• 分子量: 412.567
• InChiKey: SSDMKPSKWRMXQK-SKAQKNQVSA-N

物化性质

• 沸点：
  541.1±50.0 °C(predicted)
• 密度：
  1.08±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5S,6S,9R,10R,11R,12R,13R)-9,11-dihydroxy-3,5-(isopropylidenedioxy)-2,4,6,10,12,13-hexamethyl-8-methylenetetradecanolide 在 2,6-二甲基吡啶 、 二甲基硫 、 臭氧 作用下， 以 二氯甲烷 为溶剂， 反应 84.5h， 生成 (2R,3S,4R,5S,6S,9R,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 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：

  (S)-1-苄氧基-2-甲基戊烷-3-酮 在 palladium on activated charcoal 、 镍 盐酸 、 4-二甲氨基吡啶 、 sodium periodate 、 sodium dihydrogenphosphate 、 四氧化锇 、 2-甲基-2-丁烯 、 草酰氯 、 LiDBB 、 pH 7 buffer 、 氯代二环己基硼烷 、 lithium diethylamide 、 sodium perchlorate 、 氢气 、 双氧水 、 4-甲基苯磺酸吡啶 、 potassium hydride 、 双(三甲基硅烷基)氨基钾 、 镍 、 对甲苯磺酸 、 溶剂黄146 、 二甲基亚砜 、 N-甲基吗啉氧化物 、 三乙胺 、 tetramethylammonium triacetoxyborohydride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 173.25h， 生成 (2R,3S,4R,5S,6S,9R,10R,11R,12R,13R)-9,11-dihydroxy-3,5-(isopropylidenedioxy)-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

• Computer-assisted design and lactonization of model seco-acid derivatives of lankanolide
  作者：Tatsuo Hamada、Mitsugu Kiyokawa、Yukinari Kobayashi、Toshikazu Yoshioka、Junichiro Sano、Osamu Yonemitsu

  DOI：10.1016/j.tet.2004.03.061

  日期：2004.5

  In some cases, seco-acid derivatives (a precursor of macrolactone) did not cyclize to form the corresponding macrolactone. To design easily cyclizable seco-acid derivatives of lanaknolide, the conformation of several model seco-acids was calculated, and lactonization experiments of the seco-acids prepared from oleandomycin were carried out to elucidate the efficiency of the cyclization of the model seco-acid. The easily cyclable seco-acid was designed to be C8 exomethylene derivative of lankanolide seco-acid. On the other hand, seco-acid derivative having tertiary alcohol at C8 was predicted not to cyclize to form macrolactone. (C) 2004 Elsevier Ltd. All rights reserved.
• The first stereoselective total synthesis of lankanolide. Part 1: Computer-assisted design and lactonization of model seco-acid derivatives
  作者：Tatsuo Hamada、Yukinari Kobayashi、Mitsugu Kiyokawa、Osamu Yonemitsu

  DOI：10.1016/s0040-4039(03)00954-7

  日期：2003.6

  To design easily cyclizable seco-acid derivatives of lankanolide, the conformation of several model seco-acids was calculated and the lactonization experiments of the seco-acids were carried out to elucidate the efficiency of the cyclization of the model seco-acid. (C) 2003 Published by Elsevier Science Ltd.
• 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).