N--O-<2,3,4,6-tetrabenzyl-β-D-glucuronyl> carbamate | 168072-93-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N--O-<2,3,4,6-tetrabenzyl-β-D-glucuronyl> carbamate
• CAS: 168072-93-3
• 化学式: C₄₄H₄₉NO₁₀
• 分子量: 751.874
• InChiKey: VNQWZEZQQOMQBD-LVRDHISESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.08
• 重原子数：
  55.0
• 可旋转键数：
  19.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  127.85
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N--O-<2,3,4,6-tetrabenzyl-β-D-glucuronyl> carbamate 在 吗啉 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3S,4S,5R,6S)-3,4,5-Tris-benzyloxy-6-(3-carboxy-2,2-dimethyl-propylcarbamoyloxy)-tetrahydro-pyran-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  β-Glucuronyl carbamate based pro-moieties designed for prodrugs in ADEPT

  摘要：

  A number of pro-moieties 8a - e designed for prodrug preparation have been synthesized (chart 2). The pro-moieties, containing a glucuronyl carbamate group linked to a spacer possessing a terminal carboxylic acid group, have been synthesized from isocyanates 6 and anomerically unprotected glucuronic acids 10 (chart 2). The requisite isocyanates had to be prepared using the Curtius rearrangement. Glucuronyl carbamates proved to be excellent substrates for human beta-glucuronidase. The pro-moieties 8a - e can be coupled to hydroxy- or amino group containing drugs. The resulting prodrugs are designed to be activated by beta-glucuronidase (chart 1) and to be used in ADEPT. Application is demonstrated with the synthesis of daunomycin prodrugs 12a - e (chart 3).

  DOI：

  10.1016/0040-4039(95)00049-i
• 作为产物：
  描述：

  3,3-二甲基戊二酸酐 在 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成 N--O-<2,3,4,6-tetrabenzyl-β-D-glucuronyl> carbamate
  参考文献：
  名称：

  β-Glucuronyl carbamate based pro-moieties designed for prodrugs in ADEPT

  摘要：

  A number of pro-moieties 8a - e designed for prodrug preparation have been synthesized (chart 2). The pro-moieties, containing a glucuronyl carbamate group linked to a spacer possessing a terminal carboxylic acid group, have been synthesized from isocyanates 6 and anomerically unprotected glucuronic acids 10 (chart 2). The requisite isocyanates had to be prepared using the Curtius rearrangement. Glucuronyl carbamates proved to be excellent substrates for human beta-glucuronidase. The pro-moieties 8a - e can be coupled to hydroxy- or amino group containing drugs. The resulting prodrugs are designed to be activated by beta-glucuronidase (chart 1) and to be used in ADEPT. Application is demonstrated with the synthesis of daunomycin prodrugs 12a - e (chart 3).

  DOI：

  10.1016/0040-4039(95)00049-i

文献信息

• Synthesis and biological activity of β-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT
  作者：Dries B.A. de Bont、Ruben G.G. Leenders、Hidde J. Haisma、Ida van der Meulen-Muileman、Hans W. Scheeren

  DOI：10.1016/s0968-0896(96)00249-0

  日期：1997.2

  The syntheses of prodrugs of paclitaxel, which can be used in ADEPT in order to target paclitaxel towards tumor cells, are described. The prodrugs 1 and 2a,b consist of a spacer molecule connected via a carbamate linkage to a beta-glucuronic acid. The spacer molecule is also connected via an ester linkage to the 2'-OH of paclitaxel. Enzyme-catalyzed hydrolysis of the glucuronic acid moiety by human beta-glucuronidase results in the liberation of the parent drug paclitaxel via gamma or delta lactam formation with half-lives of 45 min and 2h (1 and 2h). The prodrugs 1 and 2b are two orders of magnitude less cytotoxic than paclitaxel. (C) 1997, Elsevier Science Ltd.