Phosphoric acid dibenzyl ester 2-(bis-benzyloxy-phosphoryloxy)-6-methoxy-3-(3,4,5-trimethoxy-benzoyl)-phenyl ester | 290347-55-6

• 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: Phosphoric acid dibenzyl ester 2-(bis-benzyloxy-phosphoryloxy)-6-methoxy-3-(3,4,5-trimethoxy-benzoyl)-phenyl ester
• 英文别名: Dibenzyl [2-bis(phenylmethoxy)phosphoryloxy-3-methoxy-6-(3,4,5-trimethoxybenzoyl)phenyl] phosphate
• CAS: 290347-55-6
• 化学式: C₄₅H₄₄O₁₃P₂
• 分子量: 854.784
• InChiKey: ZJCAZAPJEZHFCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  60
• 可旋转键数：
  22
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  144
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Phosphoric acid dibenzyl ester 2-(bis-benzyloxy-phosphoryloxy)-6-methoxy-3-(3,4,5-trimethoxy-benzoyl)-phenyl ester 在 三甲基氯硅烷 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 Phosphoric acid mono-[6-methoxy-2-phosphonooxy-3-(3,4,5-trimethoxy-benzoyl)-phenyl] ester
  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：

  3-bromo-2-formyl-6-methoxyphenyl acetate 在 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 重铬酸吡啶 、 正丁基锂 、 4 A molecular sieve 、 双氧水 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 乙腈 为溶剂， 反应 28.0h， 生成 Phosphoric acid dibenzyl ester 2-(bis-benzyloxy-phosphoryloxy)-6-methoxy-3-(3,4,5-trimethoxy-benzoyl)-phenyl ester
  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

文献信息

• Antineoplastic Agents. 443. Synthesis of the Cancer Cell Growth Inhibitor Hydroxyphenstatin and Its Sodium Diphosphate Prodrug
  作者：George R. Pettit、Matthew P. Grealish、Delbert L. Herald、Michael R. Boyd、Ernest Hamel、Robin K. Pettit

  DOI：10.1021/jm000045a

  日期：2000.7.1

  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.