1-O-acetyl-2,3,5-tri-O-benzoyl-5(R)-C-allyl-D-ribofuranose | 306960-58-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-O-acetyl-2,3,5-tri-O-benzoyl-5(R)-C-allyl-D-ribofuranose
• 英文别名: 1-O-acetyl-5(R)-C-allyl-2,3,5-tri-O-benzoyl-D-ribofuranose；[(2R,3R,4R)-5-acetyloxy-4-benzoyloxy-2-[(1R)-1-benzoyloxybut-3-enyl]oxolan-3-yl] benzoate
• CAS: 306960-58-7
• 化学式: C₃₁H₂₈O₉
• 分子量: 544.558
• InChiKey: DOENQHRRBCZHFT-FRNXGWJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-O-acetyl-2,3,5-tri-O-benzoyl-5(R)-C-allyl-D-ribofuranose 在 ammonium sulfate 、 溶剂黄146 、 六甲基二硅氮烷 、 锌 作用下， 以 间二甲苯 为溶剂， 反应 83.0h， 生成 [(2R,3R,4R,5R)-5-(4-amino-5-cyanopyrrolo[2,3-d]pyrimidin-7-yl)-4-benzoyloxy-2-[(1R)-1-benzoyloxybut-3-enyl]oxolan-3-yl] benzoate
  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：

  Benzoic acid (R)-1-((2S,3S,4R,5R)-3,4-dihydroxy-5-methoxy-tetrahydro-furan-2-yl)-but-3-enyl ester 在 硫酸 作用下， 以 吡啶 、 溶剂黄146 为溶剂， 生成 1-O-acetyl-2,3,5-tri-O-benzoyl-5(R)-C-allyl-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

• Synthesis and Cytotoxicity of 4-Amino-5-oxopyrido[2,3-<i>d</i>]pyrimidine Nucleosides
  作者：Jean-Luc Girardet、Esmir Gunic、Cathey Esler、Dariusz Cieslak、Zbigniew Pietrzkowski、Guangyi Wang

  DOI：10.1021/jm000073t

  日期：2000.10.1

  1-O-acetylated pentose sugar derivatives were condensed with silylated 4-amino-5-oxopyrido[2,3-d]pyrimidine, followed by protection, to afford a series of 4-amino-5-oxopyrido[2, 3-d]pyrimidine nucleosides. Further derivatizations provided an additional group of pyrido[2,3-d]pyrimidine nucleosides. These nucleosides were evaluated for in vitro cytotoxicity to human prostate cancer (HTB-81) and mouse melanoma

  许多核苷类似物已被临床用作抗癌药物或已在临床研究中进行了评估，而新的核苷类似物继续显示出希望。在本文中，我们报告了一系列新的吡啶并[2,3-d]嘧啶核苷的合成和细胞毒性。通过两个步骤将2-氨基-3-氰基-4-甲氧基吡啶转化为4-氨基-5-氧代吡啶并[2,3-d]嘧啶。将各种1-O-乙酰化戊糖衍生物与甲硅烷基化的4-氨基-5-氧代吡啶并[2,3-d]嘧啶缩合，然后进行保护，得到一系列的4-氨基-5-氧代吡啶并[2， 3-d]嘧啶核苷。进一步的衍生化提供了另外的吡啶基[2，3-d]嘧啶核苷基团。评估了这些核苷对人前列腺癌（HTB-81）和小鼠黑素瘤（B16）细胞以及正常人成纤维细胞（NHF）的体外细胞毒性。许多化合物（1a，b，2a-c，f，3f + 4d）对癌细胞具有明显的细胞毒性，其中4-氨基-5-氧代-8-（β-D-呋喃呋喃糖基）吡啶并[2,3- d]嘧啶（1b）是所有类型细胞中最有效的增殖抑制剂（EC（50）：0
• 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。
• Pyrrolo[2,3-d]pyrimidine nucleoside analogs
  申请人：——

  公开号：US20020035077A1

  公开（公告）日：2002-03-21

  Compositions and methods for pyrrolo[2,3-d]pyrimidine nucleoside analogs having substituents at the C4′ and C5′ positions of the ribofuranose moiety are presented. Contemplated compositions exhibit, among other things, anti-cancer and immunomodulating effects at reduced cytotoxicity.

  本发明提供了在核糖苷骨架的C4'和C5'位置具有取代基的吡咯[2,3-d]嘧啶核苷类似物的组合物和方法。考虑到的组合物在减少细胞毒性的情况下表现出抗癌和免疫调节等效果。
• PYRROLO 2,3-d]PYRIMIDINE NUCLEOSIDE ANALOGS
  申请人：ICN Pharmaceuticals, Inc.

  公开号：EP1212326A1

  公开（公告）日：2002-06-12
• EP1212326A4
  申请人：——

  公开号：EP1212326A4

  公开（公告）日：2003-08-20