(6RS,11aSR)-6-benzyloxymethyl-2-isopropyloxycarbonyl-7,8,10-trimethoxy-9-methyl-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (6RS,11aSR)-6-benzyloxymethyl-2-isopropyloxycarbonyl-7,8,10-trimethoxy-9-methyl-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione
• 英文别名: propan-2-yl (6R,11aS)-7,8,10-trimethoxy-9-methyl-1,4-dioxo-6-(phenylmethoxymethyl)-3,6,11,11a-tetrahydropyrazino[1,2-b]isoquinoline-2-carboxylate
• 化学式: C₂₈H₃₄N₂O₈
• 分子量: 526.587
• InChiKey: QILTXICYVFLPFX-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6RS,11aSR)-6-benzyloxymethyl-2-isopropyloxycarbonyl-7,8,10-trimethoxy-9-methyl-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione 在 lithium tri-t-butoxyaluminum hydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以89%的产率得到(1RS,6RS,11aSR)-6-benzyloxymethyl-1-hydroxy-2-isopropyloxycarbonyl-7,8,10-trimethoxy-9-methyl-1,2,3,6,11,11a-hexahydro-pyrazino[1,2-b]isoquinolin-4-one
  参考文献：
  名称：

  Pyrazino[1,2-b]isoquinolines: Synthesis and study of their cytostatic and cytotoxic properties

  摘要：

  The in vitro antitumor potential of novel pyrazino[1,2-b]-isoquinoline-4-ones that contain a half portion of significant natural products was explored in three cancer cell lines: MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma, and HT-29 human colon carcinoma. In general, these compounds show mid to low mu M GI(50)s, but LC(50)s over 100 mu M with the exceptions of compounds 3b and 31 that are moderately toxic in all cell lines, while compound 4a is highly toxic and selective for HT-29 cells with LC50 values in the high nanomolar range. Experiments directed to elucidate possible mechanisms of action with compounds 3a, 29, and 31 showed that compound 3a is able to efficiently induce apoptosis triggered directly from the G2/M phase of cell cycle, while compounds 29 and 31 are potentially cytostatic agents that induce the G1/S arrest of cell cycle. All three compounds do not act through DNA damage, since they do not activate this signaling at the level of sensors, transducers, and executers. Furthermore, the apoptosis induction of 3a is not mediated by activation of pro-apoptotic kinases JNK and p38 or by activation of AKT. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.083
• 作为产物：
  描述：

  (6RS,11aSR)-6-benzyloxymethyl-7,8,10-trimethoxy-9-methyl-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione 、 氯甲酸异丙酯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以98%的产率得到(6RS,11aSR)-6-benzyloxymethyl-2-isopropyloxycarbonyl-7,8,10-trimethoxy-9-methyl-2,3,11,11a-tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione
  参考文献：
  名称：

  Pyrazino[1,2-b]isoquinolines: Synthesis and study of their cytostatic and cytotoxic properties

  摘要：

  The in vitro antitumor potential of novel pyrazino[1,2-b]-isoquinoline-4-ones that contain a half portion of significant natural products was explored in three cancer cell lines: MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma, and HT-29 human colon carcinoma. In general, these compounds show mid to low mu M GI(50)s, but LC(50)s over 100 mu M with the exceptions of compounds 3b and 31 that are moderately toxic in all cell lines, while compound 4a is highly toxic and selective for HT-29 cells with LC50 values in the high nanomolar range. Experiments directed to elucidate possible mechanisms of action with compounds 3a, 29, and 31 showed that compound 3a is able to efficiently induce apoptosis triggered directly from the G2/M phase of cell cycle, while compounds 29 and 31 are potentially cytostatic agents that induce the G1/S arrest of cell cycle. All three compounds do not act through DNA damage, since they do not activate this signaling at the level of sensors, transducers, and executers. Furthermore, the apoptosis induction of 3a is not mediated by activation of pro-apoptotic kinases JNK and p38 or by activation of AKT. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.083

文献信息

• Reactions promoted by [hydroxy(tosyloxy)iodo]benzene in pyrazino[1,2–b]isoquinolines
  作者：Irene Ortín、Juan Francisco González、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/j.tet.2009.11.070

  日期：2010.1

  PhI(OH)OTs (HTIB) promoted oxidative demethylation of 1,4-hydroquinone methyl ethers to give quinones in a quantitative conversion. The efficacy of this reaction, that has been applied to simple arene compounds and to heterocyclic systems, such as 2-isopropoxycarbonyl-7,10-dimethoxy-pyrazino[1,2–b]isoquinoline-4-ones and 1,4-diones to get the corresponding 7,10-quinones (compounds 6–8), is similar to those promoted

  高价碘试剂PhI（OH）OTs（HTIB）促进了1,4-氢醌甲基醚的氧化脱甲基作用，从而在定量转化中获得了醌。该反应的功效已应用于简单的芳烃化合物和杂环体系，例如2-异丙氧基羰基-7,10-二甲氧基-吡嗪并[1,2 - b ]异喹啉-4-酮和1,4-二酮以得到相应的7,10-醌（化合物6 - 8），是类似于由CAN促进并且不需要水的存在。HTIB代替了氧化脱甲基作用，而在1-甲氧基-吡嗪并[1,2- b ]异喹啉4-ones复杂的多步过程中得到了促进，从而得到化合物9或10。
• C(3)-alkylation and cyclization of pyrazino[1,2-b]isoquinolin-4-ones
  作者：Irene Ortín、Juan Francisco González、Elena de la Cuesta、Carmen Avendaño

  DOI：10.1016/j.tet.2009.10.016

  日期：2009.11

  To avoid the epimerization of the C(11a)-stereocenter previously observed in 6,11a-cis-pyrazino[1,2-b]isoquinolin-1,4-diones, we present in this paper the C(3)-alkylation of 1-methoxy-pyrazino[1,2-b]isoquinolin-4-ones to obtain all-cis derivatives through a very reliable protocol. The success of the acid-promoted cyclization to get pentacyclic (R-3=arylmethyl) or tetracyclic (R-3=2-bromo-2-propenyl) compounds is dependent on the nature of the C(3)-unsaturated chain and of the N-substituent, but these limitations have been overcome by using trifluoromethanesulfonic as a superacid catalyst. The C-(3)-alkylation of pyrazinol 1,2-b]isoquinolin-4-one is also Studied. (C) 2009 Elsevier Ltd. All rights reserved.
• Pyrazino[1,2-b]isoquinolines: Synthesis and study of their cytostatic and cytotoxic properties
  作者：Irene Ortín、Juan Francisco González、Elena de la Cuesta、Cristina Manguan-García、Rosario Perona、Carmen Avendaño

  DOI：10.1016/j.bmc.2008.07.083

  日期：2008.10

  The in vitro antitumor potential of novel pyrazino[1,2-b]-isoquinoline-4-ones that contain a half portion of significant natural products was explored in three cancer cell lines: MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma, and HT-29 human colon carcinoma. In general, these compounds show mid to low mu M GI(50)s, but LC(50)s over 100 mu M with the exceptions of compounds 3b and 31 that are moderately toxic in all cell lines, while compound 4a is highly toxic and selective for HT-29 cells with LC50 values in the high nanomolar range. Experiments directed to elucidate possible mechanisms of action with compounds 3a, 29, and 31 showed that compound 3a is able to efficiently induce apoptosis triggered directly from the G2/M phase of cell cycle, while compounds 29 and 31 are potentially cytostatic agents that induce the G1/S arrest of cell cycle. All three compounds do not act through DNA damage, since they do not activate this signaling at the level of sensors, transducers, and executers. Furthermore, the apoptosis induction of 3a is not mediated by activation of pro-apoptotic kinases JNK and p38 or by activation of AKT. (C) 2008 Elsevier Ltd. All rights reserved.