benzyl 5-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-2,3-O-isopropylidene-β-D-ribofuranoside | 77887-00-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl 5-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-2,3-O-isopropylidene-β-D-ribofuranoside
• CAS: 77887-00-4
• 化学式: C₂₈H₃₆O₁₄
• 分子量: 596.585
• InChiKey: IIULPUDERDRSSV-XOQUHRQJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.16
• 重原子数：
  42.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  160.58
• 氢给体数：
  0.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  benzyl 5-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-2,3-O-isopropylidene-β-D-ribofuranoside 在 palladium on activated charcoal 吡啶 、 氢气 、 四氯化锡 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 25.0 ℃ 、283.71 kPa 条件下， 反应 120.83h， 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：

  (2R,3R,4R,5R)-2-(benzyloxy)-5-(hydroxymethyl)tetrahydrofuran-3,4-diyl dibenzoate 、 乙酰溴-Alpha-D-葡萄糖酮酸甲基酯 在 氰化汞 作用下， 以 硝基甲烷 、 苯 为溶剂， 以92%的产率得到benzyl 5-O-(methyl 2',3',4'-tri-O-acetyl-β-D-glucopyranosyluronate)-2,3-O-isopropylidene-β-D-ribofuranoside
  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