methyl 3-(ethoxymethoxy)-2-methoxy-6-(2'-methoxy-2'-oxoethyl)benzoate | 1198596-71-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 3-(ethoxymethoxy)-2-methoxy-6-(2'-methoxy-2'-oxoethyl)benzoate
• 英文别名: Methyl 3-(ethoxymethoxy)-2-methoxy-6-(2-methoxy-2-oxoethyl)benzoate
• CAS: 1198596-71-2
• 化学式: C₁₅H₂₀O₇
• 分子量: 312.32
• InChiKey: CGXRQGYTWWPDGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 3-(ethoxymethoxy)-2-methoxy-6-(2'-methoxy-2'-oxoethyl)benzoate 在 盐酸 、 lithium aluminium tetrahydride 、 水 、 potassium carbonate 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 生成 3,9-二甲氧基-5,8,13,13alpha-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇
  参考文献：
  名称：

  Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity

  摘要：

  Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (+/-)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (+/-)-stepholidine, were synthesized and evaluated for affinity at dopamine and sigma receptors in order to evaluate effects on D3 and sigma 2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and sigma 2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for sigma 2 receptors as well as sigma 2 versus sigma 1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and sigma receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.037
• 作为产物：
  描述：

  4-溴邻甲氧基苯酚 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 methyl 3-(ethoxymethoxy)-2-methoxy-6-(2'-methoxy-2'-oxoethyl)benzoate
  参考文献：
  名称：

  灰黄皮质激素碳骨架的合成

  摘要：

  已开发出一种合成策略，可用于获取天然产物灰黄皮质激素家族的碳骨架。关键步骤涉及酸介导的高度官能化的二羟基酮的螺环化。富电子的萘部分和吸电子的异香豆素环系统之间的微妙的电子平衡被微调以促进酸介导的螺环化反应。这种合成策略的发展为进一步研究结构更复杂的灰黄霉素天然产物提供了基础。

  DOI：

  10.1016/j.tet.2014.11.030

文献信息

• An Efficient Formal Synthesis of the Human Telomerase Inhibitor (±)-γ-Rubromycin
  作者：Dominea C. K. Rathwell、Sung-Hyun Yang、Kit Y. Tsang、Margaret A. Brimble

  DOI：10.1002/anie.200903316

  日期：2009.10.12

  in the naphthazarin and isocoumarin fragments facilitates the acid‐mediated spiroketalization step to afford the key densely functionalized spiroketal (see picture; EOM=ethoxymethyl) in the formal synthesis of (±)‐γ‐rubromycin. A novel regioselective allyloxylation/Claisen rearrangement of 2‐azido‐1,4‐naphthoquinone provides access to the highly oxygenated naphthazarin fragment.

  平衡行为：萘达沙林和异香豆素片段中电子因子的正确平衡促进了酸介导的螺酮缩合步骤，从而在（±）-γ-鲁布霉素的正式合成中提供了关键的致密功能化的螺缩酮（参见图片; EOM =乙氧基甲基）。新型的2-叠氮基1,4-萘醌的区域选择性烯丙氧基化/克莱森重排提供了进入高度氧化的萘萘沙林片段的途径。
• Dihydroxylation Studies of Isoquinolinones: Synthesis of the EF-Ring of Lysolipin I
  作者：Dirk Menche、Maximilian J. B. Heinemann、Thomas Voigt

  DOI：10.1055/a-1628-7972

  日期：2022.1

  Inspired by the potent polycyclic xanthone antibiotic lysolipin I, a general study on asymmetric dihydroxylation reactions of variously substituted isoquinolinones was performed. Different isoquinolinones were efficiently prepared, either by a Pomeranz–Fritsch type condensation or a Curtius rearrangement. Under a broad variety of conventional oxygenation procedures, they proved very unreactive. However

  受强效多环氧杂蒽酮抗生素溶血脂 I 的启发，对不同取代的异喹啉酮的不对称二羟基化反应进行了一般性研究。通过 Pomeranz-Fritsch 型缩合或 Curtius 重排，可以有效地制备不同的异喹啉酮。在各种各样的常规氧化程序下，它们被证明是非常不活泼的。然而，通过适当取代附加的芳环或更多的强制条件，最终可以进行二羟基化，这允许合成溶脂素 I 的 EF 环。
• A divergent route to 9,10-oxygenated tetrahydroprotoberberine and 8-oxoprotoberberine alkaloids: synthesis of (±)-isocorypalmine and oxypalmatine
  作者：Satishkumar Gadhiya、Shashikanth Ponnala、Wayne W. Harding

  DOI：10.1016/j.tet.2015.01.004

  日期：2015.2

  A new route which is germane to the synthesis of 9,10-oxygenated tetrahydroprotoberberines and 8-oxoprotoberberines is described. The route features the use of a diester (14) generated from reaction of dimethylmalonate with an aryl halide in the presence of n-butyllithium. The amide 17 prepared in subsequent steps is a versatile precursor for the synthesis of tetrahydroprotoberberine and 8-oxoprotoberberine

  描述了一种新的路线，该路线与9,10-氧化的四氢小pro碱和8-氧代小ber碱的合成密切相关。该路线的特征在于使用由丙二酸二甲酯在正丁基锂存在下与芳基卤化物反应生成的二酯（14）。在随后的步骤中制备的酰胺17是通用的前体，用于使用标准的高产率反应合成四氢小ber碱和8-氧小ber碱支架。以这种方式，分别以23％和22％的收率合成了（+/-）-异胭脂红和羟帕马汀。
• Synthesis of the carbon skeleton of the griseorhodins
  作者：Darcy J. Atkinson、Daniel P. Furkert、Margaret A. Brimble

  DOI：10.1016/j.tet.2014.11.030

  日期：2015.1

  A synthetic strategy to access the carbon skeleton of the griseorhodin family of natural products has been developed. The key step involved the acid-mediated spirocyclisation of a highly functionalised dihydroxyketone. The delicate electronic balance between the electron rich naphthalene moiety and the electron-withdrawing isocoumarin ring system were finely tuned to facilitate the acid-mediated spirocyclisation

  已开发出一种合成策略，可用于获取天然产物灰黄皮质激素家族的碳骨架。关键步骤涉及酸介导的高度官能化的二羟基酮的螺环化。富电子的萘部分和吸电子的异香豆素环系统之间的微妙的电子平衡被微调以促进酸介导的螺环化反应。这种合成策略的发展为进一步研究结构更复杂的灰黄霉素天然产物提供了基础。
• Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity
  作者：Satishkumar Gadhiya、Sudharshan Madapa、Thomas Kurtzman、Ian L. Alberts、Steven Ramsey、Nagavara-Kishore Pillarsetty、Teja Kalidindi、Wayne W. Harding

  DOI：10.1016/j.bmc.2016.03.037

  日期：2016.5

  Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (+/-)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (+/-)-stepholidine, were synthesized and evaluated for affinity at dopamine and sigma receptors in order to evaluate effects on D3 and sigma 2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and sigma 2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for sigma 2 receptors as well as sigma 2 versus sigma 1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and sigma receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds. (C) 2016 Elsevier Ltd. All rights reserved.