(6S,2E)-ethyl 6-methoxy-2-methyl-7-oxohept-2-enoate | 869732-11-6

• 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-oxohept-2-enoate
• 英文别名: (S,E)-ethyl 6-methoxy-2-methyl-7-oxohept-2-enoate；ethyl (E,6S)-6-methoxy-2-methyl-7-oxohept-2-enoate
• CAS: 869732-11-6
• 化学式: C₁₁H₁₈O₄
• 分子量: 214.262
• InChiKey: RMFIMAKVJBLLCM-ZKXNXJMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6S,2E)-ethyl 6-methoxy-2-methyl-7-oxohept-2-enoate 在 吡啶 、 2,6-二甲基吡啶 、 lithium hydroxide 、 copper(l) iodide 、 Schwartz's reagent 、 氯甲酸乙酯 、 potassium carbonate 、 氟化氢吡啶 、 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 130.25h， 生成 (4E,8S,9S,10E,12S,13R,14S,16R)-carbamic acid 20-(benzyloxy)-13-(methoxymethoxy)-4,10,12,16-tetramethyl-8,14,19-trimethoxy-3-oxo-2-azabicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-9-yl ester
  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：

  L-谷氨酸 在 咪唑 、 盐酸 、 草酰氯 、 dimethyl sulfide borane 、 4 A molecular sieve 、 Proton-Sponge 、 二异丁基氢化铝 、 二甲基亚砜 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 16.0h， 生成 (6S,2E)-ethyl 6-methoxy-2-methyl-7-oxohept-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。
• C15-methoxyphenylated 18-deoxy-herbimycin A analogues, their in vitro anticancer activity and heat shock protein 90 binding affinity
  作者：Zhi Zhang、Nina Xue、Chuancai Bian、Rui Yan、Longlong Jin、Xiaoguang Chen、Xiaoming Yu

  DOI：10.1016/j.bmcl.2016.07.040

  日期：2016.9

  interactions between the compound and the protein. Chemical synthesis of the target molecules were attempted by following the established synthetic route to the natural product, but resulted in the isolation of four serendipitous C15 phenylated final products. In vitro antiproliferative activity and Hsp90 binding affinity of the compounds were determined, suggesting the C18-oxygen of herbimycin A is removable

  苯醌醌沙霉素是发现热休克蛋白90（Hsp90）新型抑制剂的重要线索，该抑制剂是癌症化学疗法的有希望的靶标。由苯醌部分引起的内在肝毒性似乎严重限制了这些化合物的开发。为了通过合理的结构优化来解决该问题，基于化合物与蛋白质之间的推定相互作用，设计了一系列除草霉素A的C18-脱氧类似物。通过遵循建立的天然产物合成路线来尝试化学合成目标分子，但最终分离出了四个偶然的C15苯基化的最终产物。测定了化合物的体外抗增殖活性和Hsp90结合亲和力，
• Total synthesis of reblastatin: convenient preparation of coupling partners and scaled assembly
  作者：Chuancai Bian、Rui Yan、Xiaoming Yu

  DOI：10.1016/j.tet.2014.03.020

  日期：2014.5

  Potentially scalable total synthesis of reblastatin was achieved based on Panek's previous study. Novel and convenient synthetic routes were developed for the known C8-C20 and C1-C7 coupling partners. The challenging C8-C20 fragment was prepared from TBS protected (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (6) in nine steps (20% overall yield), and the C1-C7 fragment was synthesized from commercially available 3,4,6-tri-O-acetyl-D-glucal (9) in eight steps (35% overall yield). On a larger scale, Panek's eight-step assembly of the target molecule from the two partners was also slightly modified, giving 45 mg reblastatin (19% overall yield) in the first batch synthesis. Notable feature of our study is the settlement of the C14 chirality through a diastereoselective alpha-alkylation of 6 followed by a three-step full reduction of the lactone carboxyl, making vastly available 6 a universally applicable C11-C14 synthon for benzenoid/benzoquinone ansamycins. (C) 2014 Elsevier Ltd. All rights reserved.
• 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).
• Total Synthesis of Reblastatin
  作者：Iwona E. Wrona、Ana E. Gabarda、Gwilherm Evano、James S. Panek

  DOI：10.1021/ja055384d

  日期：2005.11.1

  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.