2-(3,4-dimethoxyphenyl)-4-{2-[2-(3,4-dimethoxyphenyl)-1-methoxycarbonylethoxycarbony]vinyl}-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid methyl ester | 55757-14-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: 2-(3,4-dimethoxyphenyl)-4-{2-[2-(3,4-dimethoxyphenyl)-1-methoxycarbonylethoxycarbony]vinyl}-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid methyl ester
• 英文别名: heptamethyl-(+)-lithospermic acid；(2S,3S)-methyl 2-(3,4-dimethoxyphenyl)-4-((E)-3-(((R)-3-(3,4-dimethoxyphenyl)-1-methoxy-1-oxopropan-2-yl)oxy)-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylate；(2S,3S)-Methyl 2-(3,4-dimethoxyphenyl)-4-{(E)-3-[(R)-3-(3,4-dimethoxyphenyl)-1-methoxy-1-oxopropan-2-yloxy]-3-oxoprop-1-enyl}-7-methoxy-2,3-dihydrobenzofuran-3-carboxylate；heptamethyl lithospermate；(10R,20S,21S)-methyl 2-(3,4-dimethoxyphenyl)-4-([3-(3,4-dimethoxyphenyl)-1-methoxy-1-oxopropan-2-yloxy]-3-oxoprop-1-enyl)-7-methoxy-2,3-dihydrobenzo[b]furan-3-carboxylate；methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-[(E)-3-[(2R)-3-(3,4-dimethoxyphenyl)-1-methoxy-1-oxopropan-2-yl]oxy-3-oxoprop-1-enyl]-7-methoxy-2,3-dihydro-1-benzofuran-3-carboxylate
• CAS: 55757-14-7
• 化学式: C₃₄H₃₆O₁₂
• 分子量: 636.653
• InChiKey: ZZTIMBQYUZALKQ-KECNHVSJSA-N

物化性质

• 熔点：
  59-64 °C
• 沸点：
  718.0±60.0 °C(Predicted)
• 密度：
  1.257±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  46
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-4-{2-[2-(3,4-dimethoxyphenyl)-1-methoxycarbonylethoxycarbony]vinyl}-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid methyl ester 在 三甲基氢氧化锡 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 20.0h， 以85%的产率得到4-{2-[1-carboxy-2-(3,4-dimethoxyphenyl)ethoxycarbonyl]vinyl}-2-(3,4-dimethoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid
  参考文献：
  名称：

  Fe催化的交叉脱氢偶联反应和Pd催化的酯导向的C H烯化反应全合成紫精酸

  摘要：

  使用两个C H活化反应作为关键步骤已完成了总精子酸的合成。铁催化的交叉脱氢偶联反应用于苯并呋喃骨架的快速构建。Pd催化的酯导向的C H烯化反应可有效组装二氢苯并呋喃酯和丙烯酸酯部分。

  DOI：

  10.1016/j.tet.2018.08.028
• 作为产物：
  描述：

  2,2-dibromo-1-(3,4-dimethoxyphenyl)ethene 在 哌啶 、 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 1-di(2-(5-methylfuryl)phosphanyl)ferrocene 、 正丁基锂 、 [RhCl(coe)2]2 、 4 A molecular sieve 、 sodium methylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 正己烷 、 氯仿 、 甲苯 、 苯 为溶剂， 反应 103.83h， 生成 2-(3,4-dimethoxyphenyl)-4-{2-[2-(3,4-dimethoxyphenyl)-1-methoxycarbonylethoxycarbony]vinyl}-7-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via Catalytic C−H Bond Activation

  摘要：

  The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C-H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C-H bond functionalization and represents the first application of this C-H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.

  DOI：

  10.1021/ja052680h

文献信息

• A Concise Route to Dihydrobenzo[<i>b</i>]furans: Formal Total Synthesis of (+)-Lithospermic Acid
  作者：Joshua Fischer、G. Paul Savage、Mark J. Coster

  DOI：10.1021/ol201130h

  日期：2011.7.1

  benzofuran reduction (Mg, MeOH, NH4Cl) provides a convergent and modular synthetic route to trans-2-aryl-2,3-dihydrobenzo[b]furan-3-carboxylates, which are a structural feature of numerous biologically active natural products. This versatile strategy was applied to the formal total synthesis of the anti-HIV natural product (+)-lithospermic acid.

  Sonogashira偶联，Pd（II）催化的羰基环化和苯并呋喃还原（Mg，MeOH，NH 4 Cl）的序列为反式-2-芳基-2,3-二氢苯并[ b ]呋喃提供了一种收敛的模块化合成途径。-3-羧酸盐，是许多具有生物活性的天然产物的结构特征。这种多用途的策略适用于抗HIV天然产物（+）-紫精酸的正式全合成。
• Synthesis of anti-HIV lithospermic acid by two diverse strategies
  作者：Tirumala G. Varadaraju、Jih Ru Hwu

  DOI：10.1039/c2ob25575h

  日期：——

  convergent route for the synthesis of the natural product (+)-lithospermic acid, which possesses anti-HIV activity, was accomplished. The (±)-trans-dihydrobenzo[b]furan core therein was prepared by two different strategies. The first strategy involved the use of a palladium-catalyzed annulation to generate an appropriately substituted benzo[b]furan ester followed by a stereoselective reduction of a carbon–carbon

  合成天然产物的有效途径 （+）-紫精酸完成了具有抗HIV活性的药物。其中的（±）-反式-二氢苯并[ b ]呋喃核是通过两种不同的策略制备的。第一个策略涉及使用钯催化的环化反应生成适当取代的苯并[ b ]呋喃酯，然后用Mg-HgCl 2-立体选择性还原碳-碳双键。甲醇。第二种策略依赖于适当取代的芳基乙酸甲酯和丁二醛之间的醛醇缩合3,4-二甲氧基苯甲醛，然后进行环化。最后，总合成（+）-紫精酸完成经由一个耦合的反式-二氢苯并[ b与对映体纯]呋喃肉桂酸乳酸甲酯。
• Highly Convergent Total Synthesis of (+)-Lithospermic Acid via a Late-Stage Intermolecular C−H Olefination
  作者：Dong-Hui Wang、Jin-Quan Yu

  DOI：10.1021/ja2010225

  日期：2011.4.20

  The total synthesis of (+)-lithospermic acid is reported, which exploits two successive C-H activation reactions as key steps. Rh-catalyzed carbene C-H insertion reaction utilizing Davies's catalyst was used to forge dihydrobenzofuran core, and a late-stage intermolecular C-H olefination coupled the olefin unit with the dihydrobenzofuran core to construct the molecule in a highly convergent manner.
• Reassignment of the Configuration of Salvianolic Acid B and Establishment of Its Identity with Lithospermic Acid B
  作者：Anja Watzke、Steven J. O'Malley、Robert G. Bergman、Jonathan A. Ellman

  DOI：10.1021/np060136w

  日期：2006.8.1

  Salvianolic acid B and lithospermic acid B are the major components of Salvia miltiorrhiza, which is one of the most popular herbal traditional medicines in Asian countries. Salvianolic acid B and lithospermic acid B are reported to have identical structures except for the configurational assignments of two stereocenters. Through chemical correlation between a degradation product of salvianolic acid B and synthetic material, the absolute configuration of salvianolic acid B has been corrected to establish that salvianolic acid B and lithospermic acid B are in fact the same compound.
• Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via Catalytic C−H Bond Activation
  作者：Steven J. O'Malley、Kian L. Tan、Anja Watzke、Robert G. Bergman、Jonathan A. Ellman

  DOI：10.1021/ja052680h

  日期：2005.10.1

  The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C-H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C-H bond functionalization and represents the first application of this C-H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.