Benzofuran-2-carboxylic acid [2-((S)-1-chloromethyl-5-hydroxy-8-methyl-1,6-dihydro-2H-pyrrolo[3,2-e]indole-3-carbonyl)-1H-indol-5-yl]-amide | 110314-47-1

• 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: Benzofuran-2-carboxylic acid [2-((S)-1-chloromethyl-5-hydroxy-8-methyl-1,6-dihydro-2H-pyrrolo[3,2-e]indole-3-carbonyl)-1H-indol-5-yl]-amide
• 英文别名: N-[2-[(8S)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydro-3H-pyrrolo[3,2-e]indole-6-carbonyl]-1H-indol-5-yl]-1-benzofuran-2-carboxamide
• CAS: 110314-47-1
• 化学式: C₃₀H₂₃ClN₄O₄
• 分子量: 538.99
• InChiKey: HARLIBQFDUUCMR-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  114
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Benzofuran-2-carboxylic acid [2-((S)-1-chloromethyl-5-hydroxy-8-methyl-1,6-dihydro-2H-pyrrolo[3,2-e]indole-3-carbonyl)-1H-indol-5-yl]-amide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以49%的产率得到adozelesin
  参考文献：
  名称：

  Novel Syntheses of Optically Active CC-1065, U-73,975(Adozelesin), U-80,244(Carzelesin), U-77,779 (Bizelesin), KW-2189, and DU-86

  摘要：

  The title syntheses were achieved by the method featuring oxidative cyclization of the enamino esters [(S)-13 and (S)-24] derived from the 5-aminoindoline [(S)-12], acylation with various structural types of indole-2-carboxylic acids, and formation of cyclopropapyrroloindole moieties.

  DOI：

  10.3987/com-97-7920
• 作为产物：
  描述：

  ((S)-5-Benzyloxy-8-methyl-1,2,3,6-tetrahydro-pyrrolo[3,2-e]indol-1-yl)-methanol 在 palladium on activated charcoal 吡啶 、 甲酸铵 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 红铝 、 lithium chloride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 Benzofuran-2-carboxylic acid [2-((S)-1-chloromethyl-5-hydroxy-8-methyl-1,6-dihydro-2H-pyrrolo[3,2-e]indole-3-carbonyl)-1H-indol-5-yl]-amide
  参考文献：
  名称：

  Coupling of cyclopropapyrroloindole (CPI) derivatives. The preparation of CC-1065, ent-CC-1065, and analogs

  摘要：

  DOI：

  10.1021/ja00256a041

文献信息

• Acid-Dependent Electrophilicity of Cyclopropylpyrroloindoles. Nature's Masking Strategy for a Potent DNA Alkylator
  作者：M. A. Warpehoski、D. E. Harper

  DOI：10.1021/ja00096a014

  日期：1994.8

  Pseudo-first-order rate constants were determined for the solvolysis of adozelesin (2) and of several related cyclopropylpyrroloindoles (CPIs) as a function of pH and buffer concentration in mixed organic-aqueous solvents. Rate constants were proportional to the hydronium ion concentration at pH > 2, and the slope of the log k(obs) vs pH plot was -1. Both the pyrrolidinoindole (2a) and piperidinoindole (2b) alcohols (ca. 4:1) were produced upon acid-catalyzed solvolysis of 2. The products and kinetic behavior are consistent with rate-determining solvent attack on the protonated CPI and competing carbocation rearrangement. Reaction of 2 with HCl afforded predominantly the pyrrolidinoindole chloride 2e, with only a trace amount (<5%) of the piperidinoindole chloride 2f. Pseudo-first-order rate constants were proportional to both chloride and hydronium ion concentration. The products and kinetic behavior are consistent with attack of chloride ion on the protonated CPI. Comparison to the reported reactivity of spiro[2.5]octa-1 ,4-dien-3-one (6) and bis(trifluoromethyl) quinone methide 8 suggests that the conjugated cyclopropyl ring of the CPI imparts a strong acid dependence to its reactivity with nucleophiles. This property may be relevant to the exceptional reactivity of the parent CPI antibiotic, CC-1065, toward duplex DNA.
• KELLY, ROBERT C.;GEBHARD, ILSE;WICNIENSKI, NANCY;ARISTOFF, PAUL A.;JOHNSO+, J. AMER. CHEM. SOC., 109,(1987) N 22, 6837-6838
  作者：KELLY, ROBERT C.、GEBHARD, ILSE、WICNIENSKI, NANCY、ARISTOFF, PAUL A.、JOHNSO+

  DOI：——

  日期：——
• US7553816B2
  申请人：——

  公开号：US7553816B2

  公开（公告）日：2009-06-30
• Novel Syntheses of Optically Active CC-1065, U-73,975(Adozelesin), U-80,244(Carzelesin), U-77,779 (Bizelesin), KW-2189, and DU-86
  作者：Yasumichi Fukuda、Hirosuke Furuta、Futoshi Shiga、Yoshikazu Asahina、Shiro Terashima

  DOI：10.3987/com-97-7920

  日期：——

  The title syntheses were achieved by the method featuring oxidative cyclization of the enamino esters [(S)-13 and (S)-24] derived from the 5-aminoindoline [(S)-12], acylation with various structural types of indole-2-carboxylic acids, and formation of cyclopropapyrroloindole moieties.
• Coupling of cyclopropapyrroloindole (CPI) derivatives. The preparation of CC-1065, ent-CC-1065, and analogs
  作者：Robert C. Kelly、Ilse Gebhard、Nancy Wicnienski、Paul A. Aristoff、Paul D. Johnson、David G. Martin

  DOI：10.1021/ja00256a041

  日期：1987.10