3-Acetyl-7-phenylmethoxychromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-Acetyl-7-phenylmethoxychromen-2-one
• 化学式: C₁₈H₁₄O₄
• 分子量: 294.307
• InChiKey: RHBTXRBCVYUTPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 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：

  3-Acetyl-7-phenylmethoxychromen-2-one 、 丙烯酸甲酯（MA） 在 silver hexafluoroantimonate 、 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 copper(II) acetate monohydrate 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 12.0h， 以55%的产率得到methyl (E)-3-(3-acetyl-7-(benzyloxy)-2-oxo-2H-chromen-4-yl)acrylate
  参考文献：
  名称：

  Access to 4-Alkenylated Coumarins via Ruthenium-Catalyzed Olefinic C–H Alkenylation of Coumarins with Modifiable and Removable Directing Groups

  摘要：

  The ruthenium-catalyzed activation of the C4 position of coumarins for coupling with acrylates was described using modifiable ketone as a directing group. The alkenylation reaction provided a direct approach to prepare previously inaccessible 4-alkenylated coumarins with operational simplicity and high atom-economy. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a tandem alkenylation/decarboxylation reaction. The potential value of this approach was further highlighted by the efficient synthesis of several heterocyclic fused coumarin derivatives.

  DOI：

  10.1021/acs.joc.0c00249
• 作为产物：
  描述：

  2,4-二羟基苯甲醛 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-Acetyl-7-phenylmethoxychromen-2-one
  参考文献：
  名称：

  Design, synthesis and anticancer activity studies of 3-(coumarin-3-yl)-acrolein derivatives: Evidenced by integrating network pharmacology and vitro assay

  摘要：

  香豆素衍生物结构多样，具有多种重要的生物活性。为了开发更有效的香豆素衍生物用于癌症治疗，我们采用分子杂交方法设计并合成了一系列香豆素-丙烯醛杂化物，并研究了它们对 A549、KB、Hela 和 MCF-7 癌细胞以及 HUVEC 和 LO2 人类正常细胞的抗增殖活性。结果表明，合成的大多数化合物对癌细胞具有显著的抑制活性，但对正常细胞的细胞毒性较低。在所有化合物中，5d 和 6e 是对不同癌细胞株最有希望的化合物，尤其是对 A549 和 KB 细胞。初步作用机理研究表明，代表化合物 6e 能够剂量依赖性地抑制迁移、侵袭和诱导细胞显著凋亡。此外，网络药理学和验证实验的综合结果表明，化合物 6e 通过 PI3K/AKT 介导的 Bcl-2 信号通路诱导线粒体依赖性凋亡。综上所述，我们的研究表明化合物 6e 可通过抑制人口腔表皮样癌细胞的 PI3K/AKT 信号通路，抑制细胞增殖、迁移、侵袭并促进细胞凋亡。这些发现证明了 3-（香豆素-3-基）-丙烯醛衍生物作为新型抗癌化疗候选药物的潜力，为进一步开发临床用药提供了思路。

  DOI：

  10.3389/fphar.2023.1141121

文献信息

• Access to 4-Alkenylated Coumarins via Ruthenium-Catalyzed Olefinic C–H Alkenylation of Coumarins with Modifiable and Removable Directing Groups
  作者：Yu-Jiao Wang、Tong-Tong Wang、Lan Yao、Qian-Long Wang、Li-Ming Zhao

  DOI：10.1021/acs.joc.0c00249

  日期：2020.8.7

  The ruthenium-catalyzed activation of the C4 position of coumarins for coupling with acrylates was described using modifiable ketone as a directing group. The alkenylation reaction provided a direct approach to prepare previously inaccessible 4-alkenylated coumarins with operational simplicity and high atom-economy. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a tandem alkenylation/decarboxylation reaction. The potential value of this approach was further highlighted by the efficient synthesis of several heterocyclic fused coumarin derivatives.
• Design, synthesis and anticancer activity studies of 3-(coumarin-3-yl)-acrolein derivatives: Evidenced by integrating network pharmacology and vitro assay
  作者：Lexian Chen、Qianqian Lv、Jianghong Cai、Jiajie Liang、Ziyan Liang、Jiahui Lin、Ying Xiao、Ruiyao Chen、Zhiling Zhang、Yue Hong、Hong Ji

  DOI：10.3389/fphar.2023.1141121

  日期：——

  Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.

  香豆素衍生物结构多样，具有多种重要的生物活性。为了开发更有效的香豆素衍生物用于癌症治疗，我们采用分子杂交方法设计并合成了一系列香豆素-丙烯醛杂化物，并研究了它们对 A549、KB、Hela 和 MCF-7 癌细胞以及 HUVEC 和 LO2 人类正常细胞的抗增殖活性。结果表明，合成的大多数化合物对癌细胞具有显著的抑制活性，但对正常细胞的细胞毒性较低。在所有化合物中，5d 和 6e 是对不同癌细胞株最有希望的化合物，尤其是对 A549 和 KB 细胞。初步作用机理研究表明，代表化合物 6e 能够剂量依赖性地抑制迁移、侵袭和诱导细胞显著凋亡。此外，网络药理学和验证实验的综合结果表明，化合物 6e 通过 PI3K/AKT 介导的 Bcl-2 信号通路诱导线粒体依赖性凋亡。综上所述，我们的研究表明化合物 6e 可通过抑制人口腔表皮样癌细胞的 PI3K/AKT 信号通路，抑制细胞增殖、迁移、侵袭并促进细胞凋亡。这些发现证明了 3-（香豆素-3-基）-丙烯醛衍生物作为新型抗癌化疗候选药物的潜力，为进一步开发临床用药提供了思路。