3',5'-di-O-acetyl-O6-benzyl-N2-[[[[4''-[(2''',3''',4'''-tri-O-acetyl-6'''-methyl-β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine | 832739-11-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 3',5'-di-O-acetyl-O6-benzyl-N2-[[[[4''-[(2''',3''',4'''-tri-O-acetyl-6'''-methyl-β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine
• 英文别名: 3',5'-di-O-acetyl-O⁶-benzyl-N²-[[[[4''-[(2''',3''',4'''-tri-O-acetyl-6'''-methyl-β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine；3',5'-di-O-acetyl-O6-benzyl-N2[[[[4''-[(2''',3''',4'''-tri-O-acetyl-6'''-methyl-β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine
• CAS: 832739-11-4
• 化学式: C₄₂H₄₄N₆O₂₀
• 分子量: 952.84
• InChiKey: GAWFUFIFPKBOOO-BHLUXPCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.92
• 重原子数：
  68.0
• 可旋转键数：
  17.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  319.79
• 氢给体数：
  1.0
• 氢受体数：
  24.0

反应信息

• 作为反应物：
  描述：

  3',5'-di-O-acetyl-O6-benzyl-N2-[[[[4''-[(2''',3''',4'''-tri-O-acetyl-6'''-methyl-β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以64%的产率得到O⁶-benzyl-N²-[[[[4''-[(β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine monosodium salt
  参考文献：
  名称：

  β-Glucuronidase-Cleavable Prodrugs of O⁶-Benzylguanine and O⁶-Benzyl-2‘-deoxyguanosine

  摘要：

  Glucuronic acid linked prodrugs of O-6-benzylguanine and O-6-benzyl-2'-deoxyguanosine were synthesized. The prodrugs were found to be quite stable at physiological pH and were more than 200-fold less active as inactivators of O-6-alkylguanine-DNA alkyltransferase (alkyltransferase) than either O-6-benzylguanine or O-6-benzyl-2'-deoxyguanosine. beta-Glucuronidase from both Escherichia coli and bovine liver cleaved the prodrugs efficiently to release O-6-benzylguanine and O-6-benzyl-2'-deoxyguanosine, respectively. In combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the prodrugs were not effective adjuvants for HT29 cell killing. However, as expected, incubation of these prodrugs with beta-glucuronidase in the culture medium led to much more efficient cell killing by BCNU as a result of the liberation of the more potent inactivators, O-6-benzylguanine and O-6-benzyl-2'-deoxyguanosine. These prodrugs may be useful for prodrug monotherapy of necrotic tumors that liberate beta-glucuronidase or for antibody-directed enzyme prodrug therapy with antibodies that can deliver beta-glucuronidase to target tumor cells.

  DOI：

  10.1021/jm0493865
• 作为产物：
  描述：

  2'-脱氧鸟苷 在 吡啶 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 96.0h， 生成 3',5'-di-O-acetyl-O6-benzyl-N2-[[[[4''-[(2''',3''',4'''-tri-O-acetyl-6'''-methyl-β-D-glucopyranuronosyl)oxy]-3''-nitrophenyl]methyl]oxy]carbonyl]-2'-deoxyguanosine
  参考文献：
  名称：

  β-Glucuronidase-Cleavable Prodrugs of O⁶-Benzylguanine and O⁶-Benzyl-2‘-deoxyguanosine

  摘要：

  Glucuronic acid linked prodrugs of O-6-benzylguanine and O-6-benzyl-2'-deoxyguanosine were synthesized. The prodrugs were found to be quite stable at physiological pH and were more than 200-fold less active as inactivators of O-6-alkylguanine-DNA alkyltransferase (alkyltransferase) than either O-6-benzylguanine or O-6-benzyl-2'-deoxyguanosine. beta-Glucuronidase from both Escherichia coli and bovine liver cleaved the prodrugs efficiently to release O-6-benzylguanine and O-6-benzyl-2'-deoxyguanosine, respectively. In combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the prodrugs were not effective adjuvants for HT29 cell killing. However, as expected, incubation of these prodrugs with beta-glucuronidase in the culture medium led to much more efficient cell killing by BCNU as a result of the liberation of the more potent inactivators, O-6-benzylguanine and O-6-benzyl-2'-deoxyguanosine. These prodrugs may be useful for prodrug monotherapy of necrotic tumors that liberate beta-glucuronidase or for antibody-directed enzyme prodrug therapy with antibodies that can deliver beta-glucuronidase to target tumor cells.

  DOI：

  10.1021/jm0493865