(+)-methyl 3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-nitro-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate | 246137-57-5

• 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: (+)-methyl 3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-nitro-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate
• 英文别名: 6-O-tert-butyl 2-O-methyl (8S)-8-(chloromethyl)-4-nitro-7,8-dihydro-3H-pyrrolo[3,2-e]indole-2,6-dicarboxylate
• CAS: 246137-57-5
• 化学式: C₁₈H₂₀ClN₃O₆
• 分子量: 409.826
• InChiKey: BUBJCQRDRASNKD-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-methyl 3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-nitro-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 (+)-methyl 1-(chloromethyl)-5-nitro-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Amino-seco-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA

  摘要：

  This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco-duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8. Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco-duocarmycin SA and the previously reported amino-seco-CBI 7, but is 15-60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.

  DOI：

  10.1021/jo990464j
• 作为产物：
  描述：

  2-碘-3-硝基-苯甲酸 在 4-二甲氨基吡啶 、 manganese(IV) oxide 、 硼酸三甲酯 、 硝酸 、 三正丁基氢锡 、 sodium hexamethyldisilazane 、 铁粉 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 甲基磺酰氯 、 三乙胺 、 lithium chloride 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 硝基甲烷 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 xylene 为溶剂， 反应 236.76h， 生成 (+)-methyl 3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-nitro-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate
  参考文献：
  名称：

  Synthesis and Cytotoxicity of Amino-seco-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA

  摘要：

  This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco-duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8. Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco-duocarmycin SA and the previously reported amino-seco-CBI 7, but is 15-60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.

  DOI：

  10.1021/jo990464j

文献信息

• Synthesis and Cytotoxicity of Amino-<i>s</i><i>eco</i>-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA
  作者：Moana Tercel、Michael A. Gieseg、William A. Denny、William R. Wilson

  DOI：10.1021/jo990464j

  日期：1999.8.1

  This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco-duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8. Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco-duocarmycin SA and the previously reported amino-seco-CBI 7, but is 15-60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.