(6S,2E)-ethyl 6-methoxy-2-methyl-7-hydroxyhept-2-enoate | 869732-22-9

• 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: (6S,2E)-ethyl 6-methoxy-2-methyl-7-hydroxyhept-2-enoate
• 英文别名: (S,E)-ethyl 7-hydroxy-6-methoxy-2-methylhept-2-enoate；ethyl (E,6S)-7-hydroxy-6-methoxy-2-methylhept-2-enoate
• CAS: 869732-22-9
• 化学式: C₁₁H₂₀O₄
• 分子量: 216.277
• InChiKey: RCSAGURSTZOCGP-ZKXNXJMVSA-N

物化性质

• 沸点：
  315.3±42.0 °C(Predicted)
• 密度：
  1.023±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6S,2E)-ethyl 6-methoxy-2-methyl-7-hydroxyhept-2-enoate 在 2,6-二甲基吡啶 、 lithium hydroxide 、 copper(l) iodide 、 Schwartz's reagent 、 草酰氯 、 氯甲酸乙酯 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 N,N'-二甲基乙二胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 97.5h， 生成 (4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-13-(methoxymethoxy)-4,10,12,16-tetramethyl-8,14,19-trimethoxy-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-one
  参考文献：
  名称：

  Total Synthesis of Reblastatin

  摘要：

  Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ja055384d
• 作为产物：
  描述：

  (2RS,5S)-5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>tetrahydrofuran-2-ol 在 盐酸 、 4 A molecular sieve 、 Proton-Sponge 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 反应 6.0h， 生成 (6S,2E)-ethyl 6-methoxy-2-methyl-7-hydroxyhept-2-enoate
  参考文献：
  名称：

  Total Synthesis of Reblastatin

  摘要：

  Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ja055384d

文献信息

• Practical synthesis of C1–8 fragment of autolytimycin via a chelation-controlled diastereoselective addition of diisopropenylzinc to α-methoxy aldehyde
  作者：Fan Yang、Liang Feng、Nengzhong Wang、Xuge Liu、Jun Li、Yuehai Shen

  DOI：10.1016/j.tet.2013.08.067

  日期：2013.11

  capable of delivering 41% overall yield at multi-gram scale. As a key step, a chelation-controlled isopropenylation of α-oxygenated aldehydes was established with a reagent combination of diisopropenylzinc, magnesium halide, and a dichloromethane/toluene mixed solvent. Cram-chelate isopropenylation products dominated for aldehydes with a small α-substituents, such as –OMe and –OBn groups, while the Felkin

  自身霉素的C1–8片段是通过可靠的10步路线合成的，该路线能够以克为单位提供41％的总收率。作为关键步骤，使用二异丙烯基锌，卤化镁和二氯甲烷/甲苯混合溶剂的试剂组合建立了α-氧化醛的螯合控制的异丙烯基化。蛤-螯合物异丙烯基化产物主要被具有少量α-取代基的醛所占据，例如–OMe和–OBn基团，而Felkin产物可以通过庞大的–OTBS基团获得。
• Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90
  作者：Iwona E. Wrona、Alexander Gozman、Tony Taldone、Gabriela Chiosis、James S. Panek

  DOI：10.1021/jo1000109

  日期：2010.5.7

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).