6-methyl-12-(β-D-glucopyranosyl)-6,7,12,13-tetrahydroindolo<2,3-a>pyrrolo<3,4-c>carbazole-5,7-dione | 172598-18-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-methyl-12-(β-D-glucopyranosyl)-6,7,12,13-tetrahydroindolo<2,3-a>pyrrolo<3,4-c>carbazole-5,7-dione
• 英文别名: 6-methyl-12-[β-D-glucopyranosyl]-6,7,12,13-tetrahydroindolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione；1,11-didechloro-6-methyl-4'-O-demethylrebeccamycin；JDC-108；6-methyl-12-(β-D-glucopyranosyl)-6,7,12,13-tetrahydroindolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione；13-methyl-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaene-12,14-dione
• CAS: 172598-18-4
• 化学式: C₂₇H₂₃N₃O₇
• 分子量: 501.496
• InChiKey: URLWTPJXRLXCMF-ANVPPWQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  37
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  148
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 6-methyl-12-(β-D-glucopyranosyl)-6,7,12,13-tetrahydroindolo<2,3-a>pyrrolo<3,4-c>carbazole-5,7-dione 以 吡啶 为溶剂， 反应 25.0h， 以83%的产率得到6-methyl-12-(β-D-2,3,4,6-tetra-O-glucopyranosyl)-6,7,12,13-tetrahydroindolo<2,3-a>pyrrolo<3,4-c>carbazole-5,7-dione
  参考文献：
  名称：

  Conformational Control in the Rebeccamycin Class of Indolocarbazole Glycosides

  摘要：

  Indolocarbazole glycosides are balanced between two conformations: a "closed" conformation containing a cyclic hydrogen bond between the indolocarbazole NH and the pyranose oxygen and an "open" conformation in which the indolocarbazole NH is hydrogen bonded to solvent. The open conformation never has a commanding advantage, even in DMSO, but in nonpolar environments the cyclic conformation predominates.

  DOI：

  10.1021/jo990296v
• 作为产物：
  描述：

  6-methyl-13-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-4b,12,12b,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 为溶剂， 以101.2 mg的产率得到6-methyl-12-(β-D-glucopyranosyl)-6,7,12,13-tetrahydroindolo<2,3-a>pyrrolo<3,4-c>carbazole-5,7-dione
  参考文献：
  名称：

  A concise approach to 1,11-didechloro-6-methyl-4′-O-demethyl rebeccamycin and its binding to human serum albumin: Fluorescence spectroscopy and molecular modeling method

  摘要：

  1,11-Didechloro-6-methyl-4'-O-demethyl rebeccamycin (JDC-108), a rebeccamycin analog possessing potent anti-tumor activities, was prepared via a concise one-pot strategy in good yield. The interaction between JDC-108 and human serum albumin (HSA) was studied by spectroscopic methods including fluorescence spectroscopy, UV-vis absorption spectrum, and molecular modeling. The quenching mechanism of fluorescence of HSA by JDC-108 was discussed. The number of binding sites n and apparent binding constant K were measured by fluorescence quenching method. The thermodynamic parameters Delta H, Delta G, Delta S at different temperatures were calculated and the results indicated the binding reaction was mainly entropy-driven and hydrophobic forces played major role in the reaction. The distance r between donor ( HSA) and acceptor (JDC-108) was obtained according to Forster theory of non-radiation energy transfer. Synchronous fluorescence and UV-vis absorption spectrum were used to investigate the molecular conformation of HSA molecules with addition of JDC-108 and the result indicated that molecular conformation of HSA molecules was changed in the presence of JDC-108 and the hydrophobic interaction played a major role in JDC-108-HSA association, which was in good agreement with the results of molecular modeling study. In addition, the effect of common ions on the binding constants of JDC-108-HSA complex was also discussed. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.017

文献信息

• Syntheses and Biological Activities of Rebeccamycin Analogues with Uncommon Sugars
  作者：Guisheng Zhang、Jie Shen、Hao Cheng、Lizhi Zhu、Lanyan Fang、Sanzhong Luo、Mark T. Muller、Gun Eui Lee、Lijun Wei、Yuguo Du、Duxin Sun、Peng George Wang

  DOI：10.1021/jm0493764

  日期：2005.4.1

  analogues with various uncommon sugars showed distinct cytotoxicities and topo I targeting activities. The activity of compounds with 2-deoxyglucose (8 and 9) > compounds with 2,6-deoxyglucose (5 and 6) > compounds with 2,3,6-deoxyglucose (10). Furthermore, the anticancer activity of compounds correlated with their ability to target endogenous topo I. These results suggest that the sugar moiety, especially

  已经合成了包含罕见糖和在酰亚胺氮上的取代的瑞贝卡霉素类似物。在结肠癌和白血病细胞中测试了它们的细胞毒性。使用Hela细胞中拓扑异构酶生物测定的体内复合物检查了它们靶向拓扑异构酶I的能力。与糖苷配基1相比，具有各种糖基的修饰化合物显示出更强的细胞毒性和topo I靶向能力。另外，具有多种罕见糖的瑞贝卡霉素类似物显示出独特的细胞毒性和topo I靶向活性。具有2-脱氧葡萄糖的化合物（8和9）>具有2,6-脱氧葡萄糖的化合物（5和6）>具有2,3,6-脱氧葡萄糖的化合物（10）的活性。此外，化合物的抗癌活性与其靶向内源性topo I的能力有关。
• Regiocontrolled Synthesis of the Antitumor Antibiotic AT2433-A1
  作者：John D. Chisholm、David L. Van Vranken

  DOI：10.1021/jo000911r

  日期：2000.11.1

  The indolo[2,3-a]carbazole glycosides are potent antitumor antibiotics currently undergoing clinical trials for the treatment of numerous types of cancer. AT2433-A1 is the most complex member of this family of compounds possessing a unique disaccharide with a sensitive aminodeoxysugar and an unsymmetric aglycon. The synthesis of this natural product requires a method for glycosylation that sets the

  吲哚[2，3-a]咔唑糖苷是有效的抗肿瘤抗生素，目前正接受临床试验以治疗多种类型的癌症。AT2433-A1是该化合物家族中最复杂的成员，具有独特的二糖以及敏感的氨基脱氧糖和不对称糖苷配基。这种天然产物的合成需要糖基化的方法，该方法设定异头异构中心的立体化学和糖苷配基的区域化学。这些目标是通过对bis-3，4-（3-吲哚基）琥珀酰亚胺进行曼尼希环化反应而得到的，主要的二氢吲哚中间体可以与复杂的碳水化合物被立体选择性地糖基化，而没有羟基的保护或活化。通过在动力学或热力学条件之间进行选择，可以精确地控制曼尼希环化反应的区域化学。该策略最终导致抗肿瘤抗生素AT2433-A1的首次合成。
• Anizon, Fabrice, Journal of Medicinal Chemistry, 1997, vol. 40, # 21, p. 3456 - 3465
  作者：Anizon, Fabrice

  DOI：——

  日期：——
• A concise approach to 1,11-didechloro-6-methyl-4′-O-demethyl rebeccamycin and its binding to human serum albumin: Fluorescence spectroscopy and molecular modeling method
  作者：Fengling Cui、Lixia Qin、Guisheng Zhang、Xiaobing Liu、Xiaojun Yao、Beilei Lei

  DOI：10.1016/j.bmc.2008.07.017

  日期：2008.8

  1,11-Didechloro-6-methyl-4'-O-demethyl rebeccamycin (JDC-108), a rebeccamycin analog possessing potent anti-tumor activities, was prepared via a concise one-pot strategy in good yield. The interaction between JDC-108 and human serum albumin (HSA) was studied by spectroscopic methods including fluorescence spectroscopy, UV-vis absorption spectrum, and molecular modeling. The quenching mechanism of fluorescence of HSA by JDC-108 was discussed. The number of binding sites n and apparent binding constant K were measured by fluorescence quenching method. The thermodynamic parameters Delta H, Delta G, Delta S at different temperatures were calculated and the results indicated the binding reaction was mainly entropy-driven and hydrophobic forces played major role in the reaction. The distance r between donor ( HSA) and acceptor (JDC-108) was obtained according to Forster theory of non-radiation energy transfer. Synchronous fluorescence and UV-vis absorption spectrum were used to investigate the molecular conformation of HSA molecules with addition of JDC-108 and the result indicated that molecular conformation of HSA molecules was changed in the presence of JDC-108 and the hydrophobic interaction played a major role in JDC-108-HSA association, which was in good agreement with the results of molecular modeling study. In addition, the effect of common ions on the binding constants of JDC-108-HSA complex was also discussed. (C) 2008 Elsevier Ltd. All rights reserved.
• Conformational Control in the Rebeccamycin Class of Indolocarbazole Glycosides
  作者：Eric J. Gilbert、John D. Chisholm、David L. Van Vranken

  DOI：10.1021/jo990296v

  日期：1999.7.1

  Indolocarbazole glycosides are balanced between two conformations: a "closed" conformation containing a cyclic hydrogen bond between the indolocarbazole NH and the pyranose oxygen and an "open" conformation in which the indolocarbazole NH is hydrogen bonded to solvent. The open conformation never has a commanding advantage, even in DMSO, but in nonpolar environments the cyclic conformation predominates.