14-(4-acetoxy-3-methoxyphenyl)-3,11-diacetoxy-2,12-dimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one | 660396-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 14-(4-acetoxy-3-methoxyphenyl)-3,11-diacetoxy-2,12-dimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
• 英文别名: lamellarin-χ；lamellarin χ triacetate；[4-(7,17-Diacetyloxy-8,16-dimethoxy-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-octaen-12-yl)-2-methoxyphenyl] acetate
• CAS: 660396-68-9
• 化学式: C₃₄H₂₉NO₁₁
• 分子量: 627.604
• InChiKey: WQLPJNHZBZVVMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  138
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  14-(4-acetoxy-3-methoxyphenyl)-3,11-diacetoxy-2,12-dimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以60%的产率得到lamellarin D triacetate
  参考文献：
  名称：

  拓扑异构酶I介导的DNA切割可作为开发源自海洋生物碱lamellarin D：掺入氨基酸残基的三酯衍生物的抗肿瘤剂的指南。

  摘要：

  近来海洋生物碱lamellarin D（LAM-D）被定性为人类拓扑异构酶I的强力毒物，赋予其对肿瘤细胞的显着细胞毒活性。我们在这里报告LAM-D系列中的第一个结构-活性关系研究。两组三酯化合物，它们在6H- [1]苯并吡喃并[4'，3'：4,5]吡咯并[2,1-a]异喹啉-6-测试了一种典型的母体生物碱的五环平面生色团作为拓扑异构酶I抑制剂。A组中的非氨基化合物对拓扑异构酶I没有活性，并且基本上无细胞毒性。与之形成鲜明对比的是，B组中掺有氨基酸残基的化合物强烈促进了人类拓扑异构酶I对DNA的切割。亮氨酸三取代的LAM-D衍生物，缬氨酸，脯氨酸，苯丙氨酸或丙氨酸残基或相关的氨基侧链可稳定拓扑异构酶I-DNA复合物。用这些分子在T向下箭头G或C向下箭头G二核苷酸处检测到的DNA切割位点与LAM-D相同，但与喜树碱仅在T向下箭头G刺激拓扑异构酶I介导的切割的DNA切割位点略有不同。在DNA弛豫

  DOI：

  10.1016/j.bmc.2004.01.020
• 作为产物：
  描述：

  2-(3-(苄氧基)-4-甲氧基苯基)乙胺 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 sodium hydride 、 碳酸氢钠 、 sodium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0 ℃ 、517.11 kPa 条件下， 反应 27.0h， 生成 14-(4-acetoxy-3-methoxyphenyl)-3,11-diacetoxy-2,12-dimethoxy-8,9-dihydro-6H-chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one
  参考文献：
  名称：

  Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings

  摘要：

  Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.

  DOI：

  10.1021/jo061810h

文献信息

• Topoisomerase I-mediated DNA cleavage as a guide to the development of antitumor agents derived from the marine alkaloid lamellarin D: triester derivatives incorporating amino acid residues
  作者：Christelle Tardy、Michaël Facompré、William Laine、Brigitte Baldeyrou、Dolores Garcı́a-Gravalos、Andrés Francesch、Cristina Mateo、Alfredo Pastor、José A Jiménez、Ignacio Manzanares、Carmen Cuevas、Christian Bailly

  DOI：10.1016/j.bmc.2004.01.020

  日期：2004.4

  pentacyclic planar chromophore typical of the parent alkaloid were tested as topoisomerase I inhibitors. The non-amino compounds in group A showed no activity against topoisomerase I and were essentially non cytotoxic. In sharp contrast, compounds in group B incorporating amino acid residues strongly promoted DNA cleavage by human topoisomerase I. LAM-D derivatives tri-substituted with leucine, valine, proline

  近来海洋生物碱lamellarin D（LAM-D）被定性为人类拓扑异构酶I的强力毒物，赋予其对肿瘤细胞的显着细胞毒活性。我们在这里报告LAM-D系列中的第一个结构-活性关系研究。两组三酯化合物，它们在6H- [1]苯并吡喃并[4'，3'：4,5]吡咯并[2,1-a]异喹啉-6-测试了一种典型的母体生物碱的五环平面生色团作为拓扑异构酶I抑制剂。A组中的非氨基化合物对拓扑异构酶I没有活性，并且基本上无细胞毒性。与之形成鲜明对比的是，B组中掺有氨基酸残基的化合物强烈促进了人类拓扑异构酶I对DNA的切割。亮氨酸三取代的LAM-D衍生物，缬氨酸，脯氨酸，苯丙氨酸或丙氨酸残基或相关的氨基侧链可稳定拓扑异构酶I-DNA复合物。用这些分子在T向下箭头G或C向下箭头G二核苷酸处检测到的DNA切割位点与LAM-D相同，但与喜树碱仅在T向下箭头G刺激拓扑异构酶I介导的切割的DNA切割位点略有不同。在DNA弛豫
• Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings
  作者：Poonsakdi Ploypradith、Thaninee Petchmanee、Poolsak Sahakitpichan、Nichole D. Litvinas、Somsak Ruchirawat

  DOI：10.1021/jo061810h

  日期：2006.12.1

  Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.