N-[4-(hydroxymethyl)-2-bromophenyl] O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate | 247075-37-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[4-(hydroxymethyl)-2-bromophenyl] O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate
• CAS: 247075-37-2
• 化学式: C₂₁H₂₄BrNO₁₂
• 分子量: 562.325
• InChiKey: GIKTWGIJCLMMCO-CBNQQXHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.18
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  172.99
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  N-[4-(hydroxymethyl)-2-bromophenyl] O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate 在 lithium hydroxide 、 Amberlite IR-120 (H⁺ form) 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 N-[4-(daunorubicin-N-carbonyloxymethyl)-2-bromophenyl] O-β-D-glucopyranuronosyl carbamate sodium salt
  参考文献：
  名称：

  Novel anthracycline-spacer-β-glucuronide, -β-glucoside, and -β-galactoside prodrugs for application in selective chemotherapy

  摘要：

  A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-beta-glycoside were designed to be activated by beta-glucuronidase or beta-galactosidase. Prodrugs with -chloro, bromo or -n-hexyl substituents on the spacer were synthesized as well as prodrugs containing a -beta-glucuronyl, -beta-glucosyl or -beta-galactosyl carbamate specifier. The key step in the synthesis of all prodrugs is the highly beta-diastereoselective addition reaction of the anomeric hydroxyl of a glycosyl donor to a spacer isocyanate resulting in the respective beta-glycosyl carbamate pro-moieties. The resulting protected pro-moieties were coupled to an anthracycline. Prodrugs were evaluated with respect to activation rate by the appropriate enzyme and additionally, their IC50 values were determined. Optimal prodrugs in this study were at least 100- to 200-fold less toxic than their corresponding drug in vitro and were activated to the parent drug in a half-life time of approximately 2 h. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00095-4
• 作为产物：
  描述：

  N-[4-(bromomethyl)-2-bromophenyl] O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate 在 水 、 silver nitrate 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以206 mg的产率得到N-[4-(hydroxymethyl)-2-bromophenyl] O-(methyl 2,3,4-tri-O-acetyl-β-D-glucopyranuronosyl) carbamate
  参考文献：
  名称：

  Novel anthracycline-spacer-β-glucuronide, -β-glucoside, and -β-galactoside prodrugs for application in selective chemotherapy

  摘要：

  A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-beta-glycoside were designed to be activated by beta-glucuronidase or beta-galactosidase. Prodrugs with -chloro, bromo or -n-hexyl substituents on the spacer were synthesized as well as prodrugs containing a -beta-glucuronyl, -beta-glucosyl or -beta-galactosyl carbamate specifier. The key step in the synthesis of all prodrugs is the highly beta-diastereoselective addition reaction of the anomeric hydroxyl of a glycosyl donor to a spacer isocyanate resulting in the respective beta-glycosyl carbamate pro-moieties. The resulting protected pro-moieties were coupled to an anthracycline. Prodrugs were evaluated with respect to activation rate by the appropriate enzyme and additionally, their IC50 values were determined. Optimal prodrugs in this study were at least 100- to 200-fold less toxic than their corresponding drug in vitro and were activated to the parent drug in a half-life time of approximately 2 h. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00095-4