2',3'-O-isopropylidene-5'-O-(methyl 2'',3'',4''-tri-O-acetyl-β-D-glucopyranosyluronate)-5-fluorouridine | 77886-90-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2',3'-O-isopropylidene-5'-O-(methyl 2'',3'',4''-tri-O-acetyl-β-D-glucopyranosyluronate)-5-fluorouridine
• CAS: 77886-90-9
• 化学式: C₂₅H₃₁FN₂O₁₅
• 分子量: 618.524
• InChiKey: RSZGUHMQJUDDHO-CNHFHXEQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  43.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  206.21
• 氢给体数：
  1.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-5'-O-(methyl 2'',3'',4''-tri-O-acetyl-β-D-glucopyranosyluronate)-5-fluorouridine 在 吡啶 、 溶剂黄146 作用下， 反应 0.5h， 生成 2',3'-di-O-acetyl-5'-O-(methyl 2'',3'',4''-tri-O-acetyl-β-D-glucopyranosyluronate)-5-fluorouridine
  参考文献：
  名称：

  Nucleosides. 114. 5'-O-Glucuronides of 5-fluorouridine and 5-fluorocytidine. Masked precursors of anticancer nucleosides

  摘要：

  5'-O-Glucuronides of anticancer nucleosides, 5-fluorouridine and 5-fluorocytidine, were synthesized by three different methods. The best preparative procedure was the one starting from benzyl 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-D-glucopyranosyluronate)-2,3-O-isopropylidene-beta-D-ribof uranoside (15) that was obtained almost quantitatively by condensation of benzyl 2,3-O-isopropylidene-beta-D-ribofuranoside (8) with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate (2). After de-O-isopropylidenation of 15, the crystalline product, benzyl 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-D-glucopyranosyluronate)-beta-D-ribofuranoside (16), was de-O-benzylated catalytically to 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-glucopyranosyluronate)-D-ribofuranose (17). Compound 17 was acetylated to crystalline 5-O-(methyl 2',3',4'-tri-O-acteyl-beta-D-glucopyranosyluronate)-1,2,3-tri-O-acetyl-beta-D-ribofuranose (18) and condensed with trimethylsilylated 5-fluorouracil of 5-fluorocytosine in the presence of SnCl4 to afford the corresponding protected nucleosides 5 and 19 in good yields. Saponification of these compounds gave 5'-O-beta-D-glucuronides of 5-fluorouridine and 5-fluorocytidine (20 and 21) isolated as their crystalline N salts. These glucuronides were substrates of both bacterial and bovine beta-glucuronidase. They were, as expected, much less toxic against several leukemia cell lines in tissue culture.

  DOI：

  10.1021/jm00139a026
• 作为产物：
  描述：

  5-氟尿嘧啶核苷 在 Dierite 、 碘 、 对甲苯磺酸 、 silver(l) oxide 作用下， 以 丙酮 、 乙腈 、 苯 为溶剂， 生成 2',3'-O-isopropylidene-5'-O-(methyl 2'',3'',4''-tri-O-acetyl-β-D-glucopyranosyluronate)-5-fluorouridine
  参考文献：
  名称：

  Nucleosides. 114. 5'-O-Glucuronides of 5-fluorouridine and 5-fluorocytidine. Masked precursors of anticancer nucleosides

  摘要：

  5'-O-Glucuronides of anticancer nucleosides, 5-fluorouridine and 5-fluorocytidine, were synthesized by three different methods. The best preparative procedure was the one starting from benzyl 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-D-glucopyranosyluronate)-2,3-O-isopropylidene-beta-D-ribof uranoside (15) that was obtained almost quantitatively by condensation of benzyl 2,3-O-isopropylidene-beta-D-ribofuranoside (8) with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate (2). After de-O-isopropylidenation of 15, the crystalline product, benzyl 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-D-glucopyranosyluronate)-beta-D-ribofuranoside (16), was de-O-benzylated catalytically to 5-O-(methyl 2', 3', 4'-tri-O-acetyl-beta-glucopyranosyluronate)-D-ribofuranose (17). Compound 17 was acetylated to crystalline 5-O-(methyl 2',3',4'-tri-O-acteyl-beta-D-glucopyranosyluronate)-1,2,3-tri-O-acetyl-beta-D-ribofuranose (18) and condensed with trimethylsilylated 5-fluorouracil of 5-fluorocytosine in the presence of SnCl4 to afford the corresponding protected nucleosides 5 and 19 in good yields. Saponification of these compounds gave 5'-O-beta-D-glucuronides of 5-fluorouridine and 5-fluorocytidine (20 and 21) isolated as their crystalline N salts. These glucuronides were substrates of both bacterial and bovine beta-glucuronidase. They were, as expected, much less toxic against several leukemia cell lines in tissue culture.

  DOI：

  10.1021/jm00139a026