(2S)-N-(2-amino-4-benzyloxy-5-methoxybenzoyl)pyrrolidine-2-carbaldehyde diethyl dithioacetal | 127810-78-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S)-N-(2-amino-4-benzyloxy-5-methoxybenzoyl)pyrrolidine-2-carbaldehyde diethyl dithioacetal
• 英文别名: [(2-amino-4-benzyloxy-5-methoxy-1,4-phenylene)carbonyl] (2S)-pyrrolidine-2-carboxaldehyde diethyldithioacetal；(2-amino-5-methoxy-4-phenylmethoxyphenyl)-[(2S)-2-[bis(ethylsulfanyl)methyl]pyrrolidin-1-yl]methanone
• CAS: 127810-78-0
• 化学式: C₂₄H₃₂N₂O₃S₂
• 分子量: 460.662
• InChiKey: MLCCLKMYGCOLJB-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.29
• 重原子数：
  31.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.79
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S)-N-(2-amino-4-benzyloxy-5-methoxybenzoyl)pyrrolidine-2-carbaldehyde diethyl dithioacetal 在 palladium on activated charcoal 1,4-环己二烯 、 calcium carbonate 、 mercury dichloride 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 27.0h， 生成 (11aS)-7-甲氧基-8-羟基-2,3,5,11ab-四氢-1H-吡咯并[2,1-c][1,4]苯并二氮杂卓-5-酮
  参考文献：
  名称：

  O-Debenzylation of a Pyrrolo[2,1-c][1,4]benzodiazepine in the Presence of a Carbinolamine Functionality: Synthesis of DC-81

  摘要：

  与其他还原方法相比，催化转移加氢法可以使含有酚羟基的吡咯并[2,1-c][1,4]苯并二氮杂卓中的酚羟基发生去苄基化反应，同时保留对生物重要的酚羟基。天然抗肿瘤抗生素 DC-81 的合成证明了这一点（10）。此外，还报道了 4-苄氧基-5-甲氧基-2-硝基苯甲酸（5）的高效合成，这是生产某些吡咯并二氮杂卓抗肿瘤药的重要中间体。

  DOI：

  10.1055/s-1990-26795
• 作为产物：
  描述：

  香草酸 在 sodium hydroxide 、 草酰氯 、 硝酸 、 四氯化锡 、 三乙胺 、 N,N-二甲基甲酰胺 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 53.25h， 生成 (2S)-N-(2-amino-4-benzyloxy-5-methoxybenzoyl)pyrrolidine-2-carbaldehyde diethyl dithioacetal
  参考文献：
  名称：

  O-Debenzylation of a Pyrrolo[2,1-c][1,4]benzodiazepine in the Presence of a Carbinolamine Functionality: Synthesis of DC-81

  摘要：

  与其他还原方法相比，催化转移加氢法可以使含有酚羟基的吡咯并[2,1-c][1,4]苯并二氮杂卓中的酚羟基发生去苄基化反应，同时保留对生物重要的酚羟基。天然抗肿瘤抗生素 DC-81 的合成证明了这一点（10）。此外，还报道了 4-苄氧基-5-甲氧基-2-硝基苯甲酸（5）的高效合成，这是生产某些吡咯并二氮杂卓抗肿瘤药的重要中间体。

  DOI：

  10.1055/s-1990-26795

文献信息

• A new convenient procedure for the synthesis of pyrrolo[2,1-c][l,4]benzodiazepines
  作者：Stephen M. Courtney、David E. Thurston

  DOI：10.1016/s0040-4039(00)73987-6

  日期：1993.8

  An efficient synthesis of the pyrrolo[2,1-c][1,4] (PBD) ring system based on a new cyclisation procedure is reported. The parent unsubstituted PBD (4a) and the benzyl derivative (4b) of the natural product DC-81 (4c) have been synthesized to illustrate the utility of this procedure.

  报告了一种基于新环化程序的吡咯并[2,1- c ] [1,4]（PBD）环系统的有效合成方法。合成了天然产物DC-81（4c）的母体未取代的PBD（4a）和苄基衍生物（4b），以说明该方法的实用性。
• PYRROLO[2, 1-C][1, 4]BENZODIAZEPINE-GLYCOSIDE PRODRUG USEFUL AS A SELECTIVE ANTI TUMOR AGENT
  申请人：Ahmed Kamal

  公开号：US20090036657A1

  公开（公告）日：2009-02-05

  The present invention provides novel pyrrolo[2,1-c][1,4]benzodiazepine-glycoside prodrug of general formula 1a-b, useful as selective anticancer agents. The present invention also provides a process for the preparation of novel pyrrolo[2,1-c][1,4]benzodiazepine-glycoside prodrugs of general formula 1a-b. This invention also provides activation of these produgs by E. coli β galactosidase and envisaged that these molecules are toxic to human cancer cell lines in the presence of the enzyme E. coli β-galactosidase. The prodrugs 1a and 1b were also found to be toxic to human cancer HepG2 cells even in the absence of the E. coli □-galactosidase. The toxic effect of the molecules when activated was similar to that of the parent molecules 6a and 6b, respectively.

  本发明提供了一种新型吡咯并[2,1-c][1,4]苯二氮杂环糖苷前药，其通用公式为1a-b，可作为选择性抗癌剂。本发明还提供了一种制备新型吡咯并[2,1-c][1,4]苯二氮杂环糖苷前药的方法，其通用公式为1a-b。本发明还提供了通过大肠杆菌β-半乳糖苷酶激活这些前药，并预期这些分子在大肠杆菌β-半乳糖苷酶存在的情况下对人类癌细胞系具有毒性。前药1a和1b甚至在没有大肠杆菌β-半乳糖苷酶的情况下也被发现对人类癌细胞HepG2具有毒性。当被激活时，这些分子的毒性效果类似于相应的母体分子6a和6b。
• Pyrrolo[2,1-c][1,4]benzodiazepine-β-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies
  作者：Ahmed Kamal、Venkatesh Tekumalla、P. Raju、V.G.M. Naidu、Prakash V. Diwan、Ramakrishna Sistla

  DOI：10.1016/j.bmcl.2008.05.038

  日期：2008.7

  Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs 15a-b, with a potential for selective therapy of solid tumors by PMT and ADEPT have been designed, synthesized and evaluated for selective cytotoxicity in the presence of the enzyme beta-glucuronidase. The prodrugs have been found to possess reduced cytotoxicity compared to the parent moieties, and are excellent substrates for the enzyme, exhibiting cytotoxicity selectively in the presence of the enzyme. Enhanced water solubility and improved stability are the other important outcomes upon modifying these molecules as their prodrugs. (C) 2008 Elsevier Ltd. All rights reserved.
• 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 enhanced reduction of nitro and azido arenes to N-arylformamides employing Zn–HCOONH4: synthesis of 4(3H)-quinazolinones and pyrrolo[2,1-c][1,4]benzodiazepines
  作者：Ahmed Kamal、K. Srinivasa Reddy、B. Rajendra Prasad、A. Hari Babu、A. Venkata Ramana

  DOI：10.1016/j.tetlet.2004.06.112

  日期：2004.8

  Microwave mediated reduction of nitro and azido arenes to N-arylformamides using Zn-HCOONH4 is described. In the absence of microwave conditions, this methodology affords amines. This protocol has been extended to the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines and 4(3H)-quinazolinones. (C) 2004 Elsevier Ltd. All rights reserved.