(2S,3S,4S,5R,6S)-3,4,5-Tris-benzyloxy-6-(3-carboxy-2,2-dimethyl-propylcarbamoyloxy)-tetrahydro-pyran-2-carboxylic acid benzyl ester | 168073-03-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3S,4S,5R,6S)-3,4,5-Tris-benzyloxy-6-(3-carboxy-2,2-dimethyl-propylcarbamoyloxy)-tetrahydro-pyran-2-carboxylic acid benzyl ester
• CAS: 168073-03-8
• 化学式: C₄₁H₄₅NO₁₀
• 分子量: 711.809
• InChiKey: KVIJBECJWRZXNQ-SYXHCOBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.44
• 重原子数：
  52.0
• 可旋转键数：
  17.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  138.85
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  紫杉醇 、 (2S,3S,4S,5R,6S)-3,4,5-Tris-benzyloxy-6-(3-carboxy-2,2-dimethyl-propylcarbamoyloxy)-tetrahydro-pyran-2-carboxylic acid benzyl ester 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-(paclitaxel-2'-O-3,3-dimethyl butanoate)-O-(2,3,4,6-tetrabenzyl-β-D-glucuronyl) carbamate
  参考文献：
  名称：

  Synthesis and biological activity of β-glucuronyl carbamate-based prodrugs of paclitaxel as potential candidates for ADEPT

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(96)00249-0
• 作为产物：
  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