thunberginol A trimethyl ether | 147666-84-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异香豆素及其衍生物
• 英文名称: thunberginol A trimethyl ether
• 英文别名: 3-(3,4-dimethoxyphenyl)-8-methoxyisocoumarin；3-(3,4-Dimethoxyphenyl)-8-methoxy-1H-2-benzopyran-1-one；3-(3,4-dimethoxyphenyl)-8-methoxyisochromen-1-one
• CAS: 147666-84-0
• 化学式: C₁₈H₁₆O₅
• 分子量: 312.322
• InChiKey: GHTACAVDDFVAHW-UHFFFAOYSA-N

物化性质

• 熔点：
  142-144 °C
• 沸点：
  493.1±45.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  thunberginol A trimethyl ether 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以98%的产率得到3-(3,4-二羟基苯基)-8-羟基异苯并吡喃-1-酮
  参考文献：
  名称：

  Palladium-catalyzed aryl halide carbonylation–intramolecular O-enolate acylation: efficient isocoumarin synthesis, including the synthesis of thunberginol A

  摘要：

  一系列α-(o-卤芳基)-取代酮在钯催化的羰基化条件下处理，导致相应异香豆素的形成。使用气球压力的CO即可实现高产率反应，且环状和非环状酮都是高效底物。这种方法的实用性通过简短合成天然产物thunberginol A得到了说明。

  DOI：

  10.1039/b917839b
• 作为产物：
  描述：

  2,2-dibromo-1-(3,4-dimethoxyphenyl)ethene 在 palladium diacetate 正丁基锂 、 甲酸 、 Grignard reagent 、 碘 、 三乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.83h， 生成 thunberginol A trimethyl ether
  参考文献：
  名称：

  New procedures for the selective synthesis of 2(2H)-pyranone derivatives and 3-aryl-4-iodoisocoumarins

  摘要：

  5-Iodo-2(2H)-pyranone derivatives have been selectively synthesized by reaction of stereodefined methyl 2-en-4-ynoates with iodine in MeCN, CH2Cl2 or C6H6 at 20degreesC (Method C) or by treatment of these esters with ICl in CH2Cl2 at 20degreesC (Method B). Methods B and C proved also to be suitable for the preparation of 3-aryl-4-iodoisocoumarins from the corresponding methyl 2-(arylethynyl)benzoates. Interestingly, the high selectivity of iodolactonization of stereodefined methyl 2-en-4-ynoates by Method B allowed preparation in moderate yields of 2(2H)-pyranone derivatives by a one-pot sequence of iodolactonization and Stille-type reactions. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)00469-6

文献信息

• Synthesis of 3-Substituted Isocoumarins and Their Inhibitory Effects on Degranulation of RBL-2H3 Cells Induced by Antigen
  作者：Ai Kurume、Yasuhiro Kamata、Masayuki Yamashita、Qilong Wang、Hisashi Matsuda、Masayuki Yoshikawa、Ikuo Kawasaki、Shunsaku Ohta

  DOI：10.1248/cpb.56.1264

  日期：——

  Eleven 3-substituted isocoumarins and a benzylidenephthalide were synthesized through thermal cyclization reaction of δ- and γ-ketoamides, respectively. Subsequent deprotection of the hydroxyl groups of the resulting isocoumarin and benzylidenephthalide compounds afforded thunberginols A, B, and F, respectively, which originated from the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO. The synthesized isocoumarins and thunberginols were evaluated for their anti-allergic activity, in which thunberginol B exhibited the highest inhibitory potency on the degranulation of RBL-2H3 cells induced by antigen. Structure–activity relationship studies were carried out to determine the necessary substituents on the 3-phenylisocoumarin skeleton for inhibitory activity.

  合成了十一种3-取代异香豆素和一个苄叉邻苯二甲酸酯，这些化合物分别通过δ-和γ-酮酰胺的热环化反应得到。随后的去保护反应使得所得的异香豆素和苄叉邻苯二甲酸酯化合物分别获得了来自紫阳花（Hydrangea macrophylla SERINGE var. thunbergii MAKINO）加工叶子的thunberginols A、B和F。合成的异香豆素和thunberginols被评估其抗过敏活性，其中thunberginol B对抗原诱导的RBL-2H3细胞去颗粒化展现了最高的抑制效力。进行了结构—活性关系研究，以确定3-苯基异香豆素骨架上抑制活性所需的取代基。
• Synthesis of 3-substituted isocoumarins and related natural products.
  作者：Shunsaku OHTA、Yasuhiro KAMATA、Takayo INAGAKI、Yukari MASUDA、Satoshi YAMAMOTO、Masayuki YAMASHITA、Ikuo KAWASAKI

  DOI：10.1248/cpb.41.1188

  日期：——

  Several N, N-diethyl-2-acylmethylbenzamides (6) were prepared from N, N-diethyl-2-toluamides (4), and the ketoamides (6) were easily cyclized to the corresponding 3-substituted isocoumarins (8) by heating in acetic acid or xylene. This simple procedure was applied to the synthesis of thunberginol A (1), thunberginol B (2), thunberginol F (14), and a key-intermediate (8j) for achlisocoumarin I (3).

  几种N,N-二乙基-2-酰基甲基苯胺（6）是从N,N-二乙基-2-甲苯酰胺（4）制备而成的，这些酮胺（6）可以通过在醋酸或二甲苯中加热轻松环化为相应的3取代异香豆素（8）。这一简单的步骤被应用于青藏醇A（1）、青藏醇B（2）、青藏醇F（14）以及达克异香豆素I（3）的一个关键中间体（8j）的合成。
• Novel One-pot Synthesis of Polysubstituted Isocoumarins from Arynes and Trifluoroacetylated β-Diketones
  作者：Kentaro Okuma、Koki Hirano、Yukiko Tanabe、Ryoichi Itoyama、Atsumi Miura、Noriyoshi Nagahora、Kosei Shioji

  DOI：10.1246/cl.131112

  日期：2014.4.5

  Polysubstituted isocoumarins such as thunberginol A were synthesized by the reaction of substituted 2-(trimethylsilyl)phenyl triflate with trifluoromethylated β-diketones in the presence of CsF. The reaction proceeded via carbon–carbon bond insertion of aryne followed by intramolecular cyclization and CF3 anion extrusion. The –C(···O)CF3 unit has high potential for not only the nucleophilic moiety but also a useful leaving group of CF3.

  多取代的异香豆素如Thunberginol A是通过在CsF存在下，将取代的2-(三甲基硅基)苯三氟甲磺酸酯与三氟甲基化的β-二酮反应合成的。该反应是通过芳基炔的碳-碳键插入，再进行分子内环化和CF3阴离子的挤出进行的。-C(···O)CF3单元不仅具有成为亲核基团的高潜力，还具有作为CF3有用离去基团的优点。
• Palladium-catalyzed aryl halide carbonylation–intramolecular O-enolate acylation: efficient isocoumarin synthesis, including the synthesis of thunberginol A
  作者：Andrew C. Tadd、Mark R. Fielding、Michael C. Willis

  DOI：10.1039/b917839b

  日期：——

  Exposure of a series of α-(o-haloaryl)-substituted ketones to palladium-catalyzed carbonylation conditions leads to the formation of the corresponding isocoumarins. Balloon pressure of CO is sufficient to achieve high yielding reactions, and both cyclic and acyclic ketones are efficient substrates. The utility of the method is illustrated by a short synthesis of the natural product thunberginol A.

  一系列α-(o-卤芳基)-取代酮在钯催化的羰基化条件下处理，导致相应异香豆素的形成。使用气球压力的CO即可实现高产率反应，且环状和非环状酮都是高效底物。这种方法的实用性通过简短合成天然产物thunberginol A得到了说明。
• Synthesis of 3-arylisocoumarins, including thunberginols A and B, unsymmetrical 3,4-disubstituted isocoumarins, and 3-ylidenephthalides via iodolactonization of methyl 2-ynylbenzoates or the corresponding carboxylic acids
  作者：Renzo Rossi、Adriano Carpita、Fabio Bellina、Paolo Stabile、Luisa Mannina

  DOI：10.1016/s0040-4020(03)00212-6

  日期：2003.3

  carboxylic acids, were used as precursors either to 3-arylisocoumarins, including naturally-occurring thunberginols A and B, or to unsymmetrical 3,4-disubstituted isocoumarins. On the other hand, (Z)- and (E)-3-iodomethylidenephthalides, which were regioselectively prepared by iodolactonization of methyl 2-ethynylbenzoate, were employed as starting materials for the stereospecific synthesis of (Z)- and

  3-芳基-4-碘异香豆素很容易通过2-甲基基苯甲酸甲酯或相应的羧酸的区域选择性碘内酯化而有效地制备，用作3-芳基异香豆素的前体，包括天然存在的类紫杉醇A和B，或不对称的。 3，4-二取代的异香豆素。另一方面，通过（2-）乙炔基苯甲酸甲酯的碘内酯化区域选择性制备的（Z）-和（E）-3-碘亚甲基萘被用作（Z）-和（E）的立体有择合成的原料。）-3-亚萘基。一些3-芳基异香豆素和不对称的3,4-二取代异香豆素在体外对人癌细胞具有一定的细胞毒活性。