(2R,11aS)-2,8-Dihydroxy-7-methoxy-1,2,3,11a-tetrahydro-10H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11-dione | 89675-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (2R,11aS)-2,8-Dihydroxy-7-methoxy-1,2,3,11a-tetrahydro-10H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11-dione
• 英文别名: (6aS,8R)-3,8-dihydroxy-2-methoxy-6a,7,8,9-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-6,11-dione
• CAS: 89675-35-4
• 化学式: C₁₃H₁₄N₂O₅
• 分子量: 278.265
• InChiKey: HDTAXVHSWJJNJJ-MUWHJKNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,11aS)-2,8-Dihydroxy-7-methoxy-1,2,3,11a-tetrahydro-10H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11-dione 在 劳森试剂 、 吡啶 、 potassium carbonate 、 氢化铝 、 汞 、 mercury dichloride 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 45.5h， 生成 (2R,11R,11aS)-2,8-diacetoxy-7,11-dimethoxy-1,2,3,11a-tetrahydro-5H-pyrrolo<2,1-c><1,4>benzodiazepin-5-one
  参考文献：
  名称：

  Bicyclic and tricyclic analogs of anthramycin

  摘要：

  As analogues of pyrrolo[2,1-c][1,4]benzodiazepine antitumor antibiotics, such as anthramycin and tomaymycin, several benzo[1,4]diazepine imines and carbinolamine ethers were prepared and tested in vivo against P388 leukemia. Two different synthetic approaches, namely, a reduction of an aromatic nitro group with a concomitant cyclization and a reduction of a lactam, were employed to generate an imine or a carbinolamine moiety. Bicyclic analogues 6a', 6f, and 6g were found to be active, indicating that the pyrroline ring of anthramycin is not an absolute necessity for the antitumor activity. Compound 6g, 3,4-dihydro-9-hydroxy-4-propargyl-5H-1,4-benzodiazepin-5-one, was at least as active as neothramycin although it was 5 times less potent. Among the tricyclic analogues, compounds 5, 7a, and 8b were active against P388 leukemia, and they generally appear to be more potent than bicyclic analogues.

  DOI：

  10.1021/jm00381a020
• 作为产物：
  描述：

  methyl (2S,4R)-4-hydroxy-1-[2-methoxy-6-nitro-4-[(4-nitrophenyl)methoxy]benzoyl]pyrrolidine-2-carboxylate 生成 (2R,11aS)-2,8-Dihydroxy-7-methoxy-1,2,3,11a-tetrahydro-10H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11-dione
  参考文献：
  名称：

  TAKUSHI, KANEKO;WONG, S. L.

  摘要：

  DOI：

文献信息

• Process for the preparation of antitumor agents
  申请人：Council of Scientific and Industrial Research

  公开号：US06362331B1

  公开（公告）日：2002-03-26

  The present invention provides a process for the preparation of a novel pyrrolo[2,1-c][1,4]benzodiazepine of formula VI wherein R is H, OII, OAc and R1 is H, and n is 3 to 5, by reacting (2S)-N-[4-hydroxy-5-methoxy-2-nitrobenzyl]-pyrrolidine-2-carboxy-carbaldehyde diethyl thioacetal with a dibromoalkane, isolating (2S)-N-[4-(3-bromoalkoxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxy carbaldehyde diethyl thioacetal so formed and reacting the isolate with a dilactam, isolating 8-{[(2S)-N-5-methoxy-2-nitrobenzoyl]pyrrolidin-2-carbaldehyde diethylthioacetal}-alkoxy-7-methoxy-2,3,5,10,11,11a-hydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11 dione, reducing the above nitro compound, isolating the 8-{[(2S)-N-5-methoxy-2-aminobenzoyl]pyrrolidin-2-carbaldehyde diethylthioacetal]-alkoxy-7-methoxy-2,3,5,10,11,11a-hydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione, reacting the amino compound above with a deprotecting agent to obtain the pyrrolo[2,1-c][1,4]benzodiazepines of formula VI wherein R, R1 and n are as stated above.

  本发明提供了一种制备新型吡咯并［2,1-c］［1,4］苯二氮平的方法，其化学式为VI，其中R为H、OII、OAc，R1为H，n为3至5，通过将（2S）-N-[4-羟基-5-甲氧基-2-硝基苯基]-吡咯烷-2-羧醛二乙硫代缩醛与二溴代烷反应，分离所形成的（2S）-N-[4-(3-溴代氧基)-5-甲氧基-2-硝基苯甲酰基]-吡咯烷-2-羧醛二乙硫代缩醛，然后将其与二内酰胺反应，分离8-［（2S）-N-5-甲氧基-2-硝基苯甲酰基］吡咯烷-2-羧醛二乙硫代缩醛］-烷氧基-7-甲氧基-2,3,5,10,11,11a-羟基-1H-吡咯并［2,1-c］［1,4］苯二氮平-5,11-二酮，还原上述硝基化合物，分离8-［（2S）-N-5-甲氧基-2-氨基苯甲酰基］吡咯烷-2-羧醛二乙硫代缩醛］-烷氧基-7-甲氧基-2,3,5,10,11,11a-羟基-1H-吡咯并［2,1-c］［1,4］苯二氮平-5,11-二酮，将上述氨基化合物与去保护剂反应以获得化学式为VI的吡咯并［2,1-c］［1,4］苯二氮平，其中R、R1和n如上所述。
• Selective reduction of aromatic azides in solution/solid-phase and resin cleavage by employing BF3·OEt2/EtSH. Preparation of DC-81
  作者：Ahmed Kamal、N. Shankaraiah、K. Laxma Reddy、V. Devaiah

  DOI：10.1016/j.tetlet.2006.04.025

  日期：2006.6

  An efficient method for the reduction of aromatic azides in both solution and solid-phase has been developed by employing (BF3OEt2)-O-./EtSH. This report also describes resin cleavage employing this reagent system. Further, this protocol has been utilized for the solution as well as the solid-phase synthesis of pyrrolo[2, 1-c][1,4]benzodiazepines, including the naturally occurring antibiotic DC-81 and fused [2,1-b]quinazolinones. (c) 2006 Elsevier Ltd. All rights reserved.
• Microwave Assisted Synthesis of Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepine-5,11-diones
  作者：Ahmed Kamal、B. S. Narayan Reddy、G. Suresh Kumar Reddy

  DOI：10.1055/s-1999-2812

  日期：1999.8
• TAKUSHI, KANEKO;WONG, S. L.
  作者：TAKUSHI, KANEKO、WONG, S. L.

  DOI：——

  日期：——
• Bicyclic and tricyclic analogs of anthramycin
  作者：T. Kaneko、H. Wong、T. W. Doyle、W. C. Rose、W. T. Bradner

  DOI：10.1021/jm00381a020

  日期：1985.3

  As analogues of pyrrolo[2,1-c][1,4]benzodiazepine antitumor antibiotics, such as anthramycin and tomaymycin, several benzo[1,4]diazepine imines and carbinolamine ethers were prepared and tested in vivo against P388 leukemia. Two different synthetic approaches, namely, a reduction of an aromatic nitro group with a concomitant cyclization and a reduction of a lactam, were employed to generate an imine or a carbinolamine moiety. Bicyclic analogues 6a', 6f, and 6g were found to be active, indicating that the pyrroline ring of anthramycin is not an absolute necessity for the antitumor activity. Compound 6g, 3,4-dihydro-9-hydroxy-4-propargyl-5H-1,4-benzodiazepin-5-one, was at least as active as neothramycin although it was 5 times less potent. Among the tricyclic analogues, compounds 5, 7a, and 8b were active against P388 leukemia, and they generally appear to be more potent than bicyclic analogues.