3,11-bis(tert-butoxycarbonyloxy)-14-[3-(tert-butoxycarbonyloxy)-4-methoxyphenyl]-2,12-dimethoxy-6H-[1]-benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one | 1454845-04-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3,11-bis(tert-butoxycarbonyloxy)-14-[3-(tert-butoxycarbonyloxy)-4-methoxyphenyl]-2,12-dimethoxy-6H-[1]-benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
• 英文别名: Tert-butyl [5-[8,16-dimethoxy-7,17-bis[(2-methylpropan-2-yl)oxycarbonyloxy]-3-oxo-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18,20-nonaen-12-yl]-2-methoxyphenyl] carbonate；tert-butyl [5-[8,16-dimethoxy-7,17-bis[(2-methylpropan-2-yl)oxycarbonyloxy]-3-oxo-4-oxa-1-azapentacyclo[11.8.0.02,11.05,10.014,19]henicosa-2(11),5,7,9,12,14,16,18,20-nonaen-12-yl]-2-methoxyphenyl] carbonate
• CAS: 1454845-04-5
• 化学式: C₄₃H₄₅NO₁₄
• 分子量: 799.829
• InChiKey: GUXNUGCTYDQBMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  58
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  165
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  8,9-Dihydro-3,11-diisopropoxy-14-(3-isopropoxy-4-methoxyphenyl)-2,12-dimethoxy-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one 在 4-二甲氨基吡啶 、 三氯化硼 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 41.0h， 生成 3,11-bis(tert-butoxycarbonyloxy)-14-[3-(tert-butoxycarbonyloxy)-4-methoxyphenyl]-2,12-dimethoxy-6H-[1]-benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  Synthesis, Resolution, and Biological Evaluation of Atropisomeric (aR)- and (aS)-16-Methyllamellarins N: Unique Effects of the Axial Chirality on the Selectivity of Protein Kinases Inhibition

  摘要：

  The total synthesis of the optically active (aR)- and (aS)-16-methyllamellarins N (3a and 3b) was achieved via resolution on HPLC chiral stationary phase. The kinase inhibitory activities of both enantiomers were evaluated on eight protein Icinases relevant to cancer and neurodegenerative diseases (CDKI/cyclin B, CDK2/cyclin A, CDK5/p25, GSK-3 alpha/beta, PIM1, DYRK1A, CLIO, and CK1). Isomer (aR)-3b exhibited potent but nonselective inhibition on all protein kinases except CK1, while (aS)-3a selectively inhibited only GSK-3 alpha/beta, PIM1, and DYRKIA. The different inhibition profiles of (aS)-3a and (aR)-3b were elucidated by docking simulation studies. Although parental lamellarin N (2) inhibited the action of topoisomerase I, both (aS)-3a and (aR)-3b showed no inhibition of this enzyme. The phenotypic scytotoxic activities of 2, (aS)-3a, and (aR)-3b on three cancer cell lines (HeLa, SH-SYSY, and IMR32) changed according to their topoisomerase I and protein kinase inhibitory activities.

  DOI：

  10.1021/jm400719y

文献信息

• Synthesis, Resolution, and Biological Evaluation of Atropisomeric (a<i>R</i>)- and (a<i>S</i>)-16-Methyllamellarins N: Unique Effects of the Axial Chirality on the Selectivity of Protein Kinases Inhibition
  作者：Kenyu Yoshida、Ryosuke Itoyama、Masashi Yamahira、Junji Tanaka、Nadège Loaëc、Olivier Lozach、Emilie Durieu、Tsutomu Fukuda、Fumito Ishibashi、Laurent Meijer、Masatomo Iwao

  DOI：10.1021/jm400719y

  日期：2013.9.26

  The total synthesis of the optically active (aR)- and (aS)-16-methyllamellarins N (3a and 3b) was achieved via resolution on HPLC chiral stationary phase. The kinase inhibitory activities of both enantiomers were evaluated on eight protein Icinases relevant to cancer and neurodegenerative diseases (CDKI/cyclin B, CDK2/cyclin A, CDK5/p25, GSK-3 alpha/beta, PIM1, DYRK1A, CLIO, and CK1). Isomer (aR)-3b exhibited potent but nonselective inhibition on all protein kinases except CK1, while (aS)-3a selectively inhibited only GSK-3 alpha/beta, PIM1, and DYRKIA. The different inhibition profiles of (aS)-3a and (aR)-3b were elucidated by docking simulation studies. Although parental lamellarin N (2) inhibited the action of topoisomerase I, both (aS)-3a and (aR)-3b showed no inhibition of this enzyme. The phenotypic scytotoxic activities of 2, (aS)-3a, and (aR)-3b on three cancer cell lines (HeLa, SH-SYSY, and IMR32) changed according to their topoisomerase I and protein kinase inhibitory activities.