1’,2’,3’-trimethoxybenzo[5’,6’:5,4]-1H-1-oxo-6,7-dihydrocyclohepta[3,2-f]-2’’-acetoxymethylbenzofuran

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 1’,2’,3’-trimethoxybenzo[5’,6’:5,4]-1H-1-oxo-6,7-dihydrocyclohepta[3,2-f]-2’’-acetoxymethylbenzofuran
• 英文别名: (3,4,5-Trimethoxy-10-oxo-14-oxatetracyclo[9.7.0.02,7.013,17]octadeca-1(11),2,4,6,12,15,17-heptaen-15-yl)methyl acetate；(3,4,5-trimethoxy-10-oxo-14-oxatetracyclo[9.7.0.02,7.013,17]octadeca-1(11),2,4,6,12,15,17-heptaen-15-yl)methyl acetate
• 化学式: C₂₃H₂₂O₇
• 分子量: 410.423
• InChiKey: BYMLZMDLURXSDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  84.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1’,2’,3’-trimethoxybenzo[5’,6’:5,4]-1H-1-oxo-6,7-dihydrocyclohepta[3,2-f]-2’’-acetoxymethylbenzofuran 、 trimethylphosphonium acetate 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以47 %的产率得到1',2',3'-trimethoxybenzo[5',6':5,4]-1H-1-methoxycarbonylmethylene-6,7-dihydroxy-cyclohepta[3,2-f]-2''-hydroxymethylbenzofuran
  参考文献：
  名称：

  新型 C-7 亚甲基呋喃类化合物的设计、合成及体外生物活性

  摘要：

  通过 Wittig、Horner-Wadsworth-Emmons 和 Nenajdenko-Shastin 烯烃化方法合成了一系列带有 C-7 亚甲基片段的新型杂环秋水仙碱衍生物。使用 MTT 测定和细胞周期分析研究了最有前途的化合物的体外生物活性。在亚甲基片段上具有吸电子基团的化合物对 COLO-357、BxPC-3、HaCaT、PANC-1 和 A549 细胞系表现出显着的抗增殖活性。双键上取代基的空间取向显着影响其生物活性。

  DOI：

  10.3390/pharmaceutics15041034
• 作为产物：
  描述：

  秋水仙碱 在 盐酸 、 4-二甲氨基吡啶 、 copper(l) iodide 、 N-methyl-4-formylpyridinium benzolsulfonate 、 水 、 碘 、 sodium methylate 、 potassium acetate 、 palladium diacetate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 sodium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 56.0h， 生成 1’,2’,3’-trimethoxybenzo[5’,6’:5,4]-1H-1-oxo-6,7-dihydrocyclohepta[3,2-f]-2’’-acetoxymethylbenzofuran
  参考文献：
  名称：

  Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids

  摘要：

  A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect). 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.020

文献信息

• Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids
  作者：Iuliia A. Gracheva、Iuliia V. Voitovich、Vladimir I. Faerman、Nikolay S. Sitnikov、Ekaterina V. Myrsikova、Hans-Gunther Schmalz、Elena V. Svirshevskaya、Alexey Yu Fedorov

  DOI：10.1016/j.ejmech.2016.11.020

  日期：2017.1

  A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect). 2016 Elsevier Masson SAS. All rights reserved.
• Design, Synthesis and In Vitro Biological Activity of Novel C-7 Methylene Congeners of Furanoallocolchicinoids
  作者：Iuliia A. Gracheva、Elena V. Svirshchevskaya、Ekaterina S. Shchegravina、Yulia B. Malysheva、Alsu R. Sitdikova、Alexey Yu. Fedorov

  DOI：10.3390/pharmaceutics15041034

  日期：——

  A series of novel heterocyclic colchicine derivatives bearing a C-7 methylene fragment were synthesized via Wittig, Horner–Wadsworth–Emmons and Nenajdenko–Shastin olefination approaches. The in vitro biological activities of the most promising compounds were investigated using MTT assays and cell cycle analyses. Compounds with an electron withdrawing group on the methylene fragment exhibited substantial

  通过 Wittig、Horner-Wadsworth-Emmons 和 Nenajdenko-Shastin 烯烃化方法合成了一系列带有 C-7 亚甲基片段的新型杂环秋水仙碱衍生物。使用 MTT 测定和细胞周期分析研究了最有前途的化合物的体外生物活性。在亚甲基片段上具有吸电子基团的化合物对 COLO-357、BxPC-3、HaCaT、PANC-1 和 A549 细胞系表现出显着的抗增殖活性。双键上取代基的空间取向显着影响其生物活性。