5-O-(4,4'-dimethoxytrityl)-4-C-formyl-2,3-O-isopropylidene-1-O-methyl-β-D-ribofuranose | 327614-88-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5-O-(4,4'-dimethoxytrityl)-4-C-formyl-2,3-O-isopropylidene-1-O-methyl-β-D-ribofuranose
• 英文别名: (3aS,4R,6R,6aR)-4-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-6-methoxy-2,2-dimethyl-6,6a-dihydro-3aH-furo[3,4-d][1,3]dioxole-4-carbaldehyde
• CAS: 327614-88-0
• 化学式: C₃₁H₃₄O₈
• 分子量: 534.606
• InChiKey: AYIRROBYCZYPID-JZGWFFLPSA-N

物化性质

• 沸点：
  632.2±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-O-(4,4'-dimethoxytrityl)-4-C-formyl-2,3-O-isopropylidene-1-O-methyl-β-D-ribofuranose 在 palladium on activated charcoal ammonium sulfate 、 硫酸 、 氨 、 氢气 、 sodium pentanolate 、 三乙胺 、 六甲基二硅氮烷 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 吡啶 、 甲醇 、 乙醚 、 溶剂黄146 、 乙酸乙酯 、 间二甲苯 、 苯 为溶剂， 120.0 ℃ 、137.9 kPa 条件下， 反应 105.5h， 生成 4-amino-5-cyano-7-(4-C-ethyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis and cytotoxicity of 4′-C- and 5′-C-substituted toyocamycins

  摘要：

  Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and T-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]py (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound le showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00221-2
• 作为产物：
  描述：

  ((3aS,6R,6aR)-6-甲氧基-2,2-二甲基四氢呋喃并[3,4-d][1,3]二氧杂环戊烯-4,4-二基)二甲醇 在 N,N'-二环己基碳二亚胺 吡啶 、 二甲基亚砜 、 三氟乙酸 作用下， 以 吡啶 、 甲苯 为溶剂， 反应 8.0h， 生成 5-O-(4,4'-dimethoxytrityl)-4-C-formyl-2,3-O-isopropylidene-1-O-methyl-β-D-ribofuranose
  参考文献：
  名称：

  Synthesis and cytotoxicity of 4′-C- and 5′-C-substituted toyocamycins

  摘要：

  Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and T-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]py (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound le showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00221-2

文献信息

• Pyrido[2,3-d]pyrimidine and pyrimido[4,5-d]pyrimidine nucleosides
  申请人：——

  公开号：US20030144502A1

  公开（公告）日：2003-07-31

  A purine nucleoside analog includes a pyrido[2,3-d]pyrimidine or a pyrimido[4,5-d]pyrimidine and further has a sugar moiety that is optionally modified at the C2′, C3′, C4′ and/or C5′ position. Particularly contemplated compounds also include prodrug forms of the purine nucleoside analogs, and both purine nucleoside analogs and the corresponding prodrugs are employed in the reduction of growth of neoplastic cells.

  一种嘌呤核苷类似物包括吡啶并［2,3-d］嘧啶或嘧啶并［4,5-d］嘧啶，进一步具有一个糖基团，在C2′、C3′、C4′和/或C5′位置可以选择性地被修饰。特别考虑的化合物还包括嘌呤核苷类似物的前药形式，嘌呤核苷类似物和相应的前药都用于抑制肿瘤细胞的生长。
• US7081449B2
  申请人：——

  公开号：US7081449B2

  公开（公告）日：2006-07-25
• Synthesis and cytotoxicity of 4′-C- and 5′-C-substituted toyocamycins
  作者：Esmir Gunic、Jean-Luc Girardet、Zbigniew Pietrzkowski、Cathey Esler、Guangyi Wang

  DOI：10.1016/s0968-0896(00)00221-2

  日期：2001.1

  Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and T-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]py (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound le showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly. (C) 2000 Elsevier Science Ltd. All rights reserved.