benzyl [2-(N-chloroformyl-N-methylamino)-4-nitrophenyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-β-D-glucopyranoside]uronate | 355010-37-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl [2-(N-chloroformyl-N-methylamino)-4-nitrophenyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-β-D-glucopyranoside]uronate
• 英文别名: benzyl [2-(N-chloroformyl-N-methylamino)-4-nitrophenyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-β-D-glucopyranosid]uronate；benzyl (2S,3R,4S,5R,6S)-3,4,5-tris[[tert-butyl(dimethyl)silyl]oxy]-6-[2-[carbonochloridoyl(methyl)amino]-4-nitrophenoxy]oxane-2-carboxylate
• CAS: 355010-37-6
• 化学式: C₃₉H₆₃ClN₂O₁₀Si₃
• 分子量: 839.646
• InChiKey: HTFVHDCYVWCRIT-MNYCWKMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.41
• 重原子数：
  55
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  139
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  依托泊苷 、 benzyl [2-(N-chloroformyl-N-methylamino)-4-nitrophenyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-β-D-glucopyranoside]uronate 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以57%的产率得到benzyl [4-nitrophenyl-2-[(etoposide-4'-O-carbonyl)methyl-amino]-2,3,4-tri-O-(tert-butyldimethylsilyl)-β-D-glucopyranosid]uronate
  参考文献：
  名称：

  Prodrug Mono therapy: synthesis and biological evaluation of an etoposide glucuronide-prodrug

  摘要：

  A glucuronide-based prodrug of etoposide has been synthesized for a Prodrug Mono Therapy strategy. The aim is to selectively liberate the active compound by beta-D-glucuronidase already present in necrotic tumours. Outside from these sites, this enzyme is known to be localised inside the lysosomes. The three components of this prodrug are the glucuronic acid (substrate of the enzyme), the spacer (for a faster cleavage), and the active etoposide. In vitro, the prodrug was shown to be less cytotoxic and more water-soluble than etoposide itself. Finally, in the presence of the beta-D-glucuronidase, cleavage of the prodrug with complete release of the drug has been observed. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00108-1
• 作为产物：
  描述：

  (2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(2-(methylamino)-4-nitrophenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 4-二甲氨基吡啶 、 sodium hydroxide 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 、 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 60.58h， 生成 benzyl [2-(N-chloroformyl-N-methylamino)-4-nitrophenyl-2,3,4-tri-O-(tert-butyldimethylsilyl)-β-D-glucopyranoside]uronate
  参考文献：
  名称：

  癌症化疗：一种用于 ADEPT（抗体导向的酶前药治疗）的紫杉醇前药

  摘要：

  已经合成了一种基于葡萄糖醛酸苷的紫杉醇前药 (taxol®)，用于抗体导向酶前药治疗 (ADEPT)。这种三组分前药是通过将 N-甲基氨基 4-硝基苯酚 (10) 的葡萄糖醛酸衍生物通过芳香族氨基甲酸酯偶联到紫杉醇侧链的 2'-羟基上而获得的。一旦脱保护，前药 2 显示在人血清中相对稳定，并且细胞毒性（IC50 分别为 65 μM 和 90 nM）显着低于母体药物。正如预期的那样，化合物 2 在 β-葡萄糖醛酸酶存在下有效地释放紫杉醇。

  DOI：

  10.1002/1099-0690(200106)2001:11<2129::aid-ejoc2129>3.0.co;2-#

文献信息

• Prodrug Mono therapy: synthesis and biological evaluation of an etoposide glucuronide-prodrug
  作者：Frédéric Schmidt、Claude Monneret

  DOI：10.1016/s0968-0896(03)00108-1

  日期：2003.5

  A glucuronide-based prodrug of etoposide has been synthesized for a Prodrug Mono Therapy strategy. The aim is to selectively liberate the active compound by beta-D-glucuronidase already present in necrotic tumours. Outside from these sites, this enzyme is known to be localised inside the lysosomes. The three components of this prodrug are the glucuronic acid (substrate of the enzyme), the spacer (for a faster cleavage), and the active etoposide. In vitro, the prodrug was shown to be less cytotoxic and more water-soluble than etoposide itself. Finally, in the presence of the beta-D-glucuronidase, cleavage of the prodrug with complete release of the drug has been observed. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Cancer Chemotherapy: A Paclitaxel Prodrug for ADEPT (Antibody‐Directed Enzyme Prodrug Therapy)
  作者：Frédéric Schmidt、Ioana Ungureanu、Romain Duval、Alain Pompon、Claude Monneret

  DOI：10.1002/1099-0690(200106)2001:11<2129::aid-ejoc2129>3.0.co;2-#

  日期：2001.6

  A glucuronide-based prodrug of paclitaxel (taxol®) has been synthesized for use in antibody-directed enzyme prodrug therapy (ADEPT). This three-component prodrug was obtained by coupling a glucuronyl derivative of N-methylamino 4-nitrophenol (10) to the 2′-hydroxy group of the side-chain of paclitaxel through an aromatic carbamate. Once deprotected, prodrug 2 was shown to be relatively stable in human

  已经合成了一种基于葡萄糖醛酸苷的紫杉醇前药 (taxol®)，用于抗体导向酶前药治疗 (ADEPT)。这种三组分前药是通过将 N-甲基氨基 4-硝基苯酚 (10) 的葡萄糖醛酸衍生物通过芳香族氨基甲酸酯偶联到紫杉醇侧链的 2'-羟基上而获得的。一旦脱保护，前药 2 显示在人血清中相对稳定，并且细胞毒性（IC50 分别为 65 μM 和 90 nM）显着低于母体药物。正如预期的那样，化合物 2 在 β-葡萄糖醛酸酶存在下有效地释放紫杉醇。