1-溴-4-甲氧基-2,3-二(甲氧基甲氧基)-苯 | 290347-62-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 1-溴-4-甲氧基-2,3-二(甲氧基甲氧基)-苯
• 英文名称: 1-bromo-4-methoxy-2,3-bis(methoxymethoxy)-benzene
• 英文别名: 1-bromo-2,3-bis(methoxymethoxy)-4-methoxybenzene；1-bromo-4-methoxy-2,3-bis(methoxymethoxy)benzene；1-Bromo-2,3-bis(methoxymethyloxy)-4-methoxy-benzene
• CAS: 290347-62-5
• 化学式: C₁₁H₁₅BrO₅
• 分子量: 307.141
• InChiKey: VYURZSCBTPPIES-UHFFFAOYSA-N

物化性质

• 沸点：
  344.7±42.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-溴-4-甲氧基-2,3-二(甲氧基甲氧基)-苯 在 盐酸 、 重铬酸吡啶 、 正丁基锂 、 4 A molecular sieve 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 hydroxyphenstatin
  参考文献：
  名称：

  Antineoplastic Agents. 443. Synthesis of the Cancer Cell Growth Inhibitor Hydroxyphenstatin and Its Sodium Diphosphate Prodrug

  摘要：

  A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the discovery of a potent cancer cell growth inhibitor designated phenstatin (5a). This benzophenone derivative of combretastatin A-4 showed remarkable antineoplastic activity, and the benzophenone derivative of combretastatin A-1 was therefore synthesized. The benzophenone, designated hydroxyphenstatin (6a), was synthesized by coupling of a protected bromobenzene and a benzaldehyde to give the benzhydrol with subsequent oxidation to the ketone. Hydroxyphenstatin was converted to the sodium phosphate prodrug (6e) by a dibenzyl phosphite phosphorylation and subsequent benzyl cleavage (6a --> 6d --> 6e). While hydroxyphenstatin (6a) was a potent inhibitor of tubulin polymerization with activity comparable to that of combretastatin A-1 (3a), the phosphorylated derivative (6e) was inactive.

  DOI：

  10.1021/jm000045a
• 作为产物：
  描述：

  5-溴-2-甲氧基苯酚 在 聚合甲醛 、 三乙胺 、 N,N-二异丙基乙胺 、 magnesium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 1-溴-4-甲氧基-2,3-二(甲氧基甲氧基)-苯
  参考文献：
  名称：

  Synthesis of combretastatins A-1 and B-1

  摘要：

  Combretastatins A-1 and B-1 have been synthesized by coupling MOM-protected p-iodomethoxycatechol with 3,4,5-trimethoxyphenylacetylene in a Sonogashira reaction. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.12.037

文献信息

• Hydroxyphenstatin and the prodrugs thereof
  申请人：——

  公开号：US20030220304A1

  公开（公告）日：2003-11-27

  The benzophenone derivative of combretastatin A-1, designated “hydroxyphenstatin”, was synthesized by compiling a protected bromobenzene and a benzaldehyde to form a benzhydrol which was subsequently oxidized to the ketone. Hydroxyphenstatin was converted to a sodium phosphate prodrug by dibenzyl phosphite phosphorylation and subsequent benzyl cleavage: Hydroxyphenstatin and the prodrugs thereof were found to be a potent inhibitor of tubulin polymerization and to demonstrate surprisingly effective anti neoplastic activity against a series of human cancer cells and murine P388 lymphocytic leukemia cells.

  将康柏乙烯A-1的苯甲酮衍生物命名为“羟基苯基苯甲酮”，通过组合保护溴苯和苯甲醛合成苯并醇，随后氧化为酮。通过二苯基磷酸酯磷酸化和随后的苄基裂解，将羟基苯基苯甲酮转化为磷酸钠前药。发现羟基苯基苯甲酮及其前药是强效的微管聚合抑制剂，并对一系列人类癌细胞和小鼠P388淋巴细胞白血病细胞表现出惊人的有效抗肿瘤活性。
• Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1
  作者：Øyvind W. Akselsen、Kristin Odlo、Jing-Jy Cheng、Giorgio Maccari、Maurizio Botta、Trond Vidar Hansen

  DOI：10.1016/j.bmc.2011.11.010

  日期：2012.1

  3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diamine (8) and 5-(2,3-difluoro-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (9) were the three most active compounds regarding inhibition of both tubulin polymerization and angiogenesis. Molecular modeling studies revealed that combretastatins 1 and 2 and analogs 5–11 could be successfully docked into the colchicine

  康布雷他汀A-1的7个1,5-二取代1,2,3-三唑类似物和2个1,4-二取代1,2,3-三唑类似物的合成，细胞毒性，微管蛋白聚合数据抑制和抗血管生成作用（1）在本文中报道。生物学研究表明1,5-二取代1,2,3-三唑3-甲氧基-6-（1-（3,4,5-三甲氧基苯基）-1 H -1,2,3-三唑-5-基）苯-1,2-二醇（6），3-甲氧基-6-（1-（3,4,5-三甲氧基苯基）-1 H -1,2,3-三唑-5-基）苯-1 ，2-二胺（8）和5-（2,3-二氟-4-甲氧基苯基）-1-（3,4,5-三甲氧基苯基）-1 H -1,2,3-三唑（9）是有关抑制微管蛋白聚合和血管生成的三种活性最高的化合物。分子模拟研究表明，考布他汀1和2以及类似物5 - 11可以成功对接为α，β -微管蛋白的秋水仙碱结合位点。
• Direct biooxidation of arenes to corresponding catechols with E. coli JM109 (pDTG602). Application to synthesis of combretastatins A-1 and B-1
  作者：Vu P Bui、Tomas Hudlicky、Trond V Hansen、Yngve Stenstrom

  DOI：10.1016/s0040-4039(02)00389-1

  日期：2002.4

  Convergent syntheses of combretastatins A-1 and B-1 were accomplished via coupling of biocatalytically generated p-bromomethoxycatechol with trimethoxyphenylacetylene. (C) 2002 Elsevier Science Ltd. All rights reserved.
• US6777578B2
  申请人：——

  公开号：US6777578B2

  公开（公告）日：2004-08-17