2',3',5'-tri-O-benzoylinosine | 6741-88-4

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3',5'-tri-O-benzoylinosine
• 英文别名: 2^'^,3^'^,5^'^-Tri-O-Benzoylinosine；[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]methyl benzoate
• CAS: 6741-88-4
• 化学式: C₃₁H₂₄N₄O₈
• 分子量: 580.554
• InChiKey: HYIROYSRWYWYBO-ZYWWQZICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2',3',5'-tri-O-benzoylinosine 在 镍 劳森试剂 、 sodium hydroxide 作用下， 以 吡啶 、 甲醇 、 水 为溶剂， 反应 12.08h， 生成 9 - (Β-D -呋喃核糖)嘌呤
  参考文献：
  名称：

  Synthesis and Stability of GNRA-Loop Analogs

  摘要：

  DOI：

  10.1002/(sici)1522-2675(19991215)82:12<2094::aid-hlca2094>3.0.co;2-h
• 作为产物：
  描述：

  6-chloro-9-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)purine 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 2',3',5'-tri-O-benzoylinosine
  参考文献：
  名称：

  Oxidative transformations of minor components of nucleic acids. An anomalous reaction course of oxidation of N6,N6-dialkyladenosines and related compounds with m-chloroperoxybenzoic acid

  摘要：

  DOI：

  10.1021/jo00244a010

文献信息

• Syntheses of N4,2',3',5'-tetraacylcytidines from N4-acylcytosines, via condensation with tetraacylribose and transribosylation with acylated purine nucleosides.
  作者：YOSHIHIRO SUGIURA、SYUICHI FURUYA、YOSHIYASU FURUKAWA

  DOI：10.1248/cpb.36.3253

  日期：——

  N4-Isobutyryl- and -(2-ethylhexanoyl)cytosines (Ia, b) were synthesized by acylation of cytosine. N4, 2', 3', 5'-Tetraacylcytidines (III) were synthesized by two methods involving stannic chloride catalysis. One involeves condensation of N4-acylcytosines (I) and 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-D-ribofuranose (II), and the other involves transribosylation between N4-acylcytosines and acyl-inosines or -guanosines (IVa-d). N4-Octanoyl-2', 3', 5'-triacetylcytidine (IIIf) waS converted into cytidine by deacylation in a good yield.

  N4-异丁酰基和-(2-乙基己酰基)胞嘧啶(Ia, b)是通过对胞嘧啶进行酰化反应合成的。N4, 2', 3', 5'-四酰基胞苷(III)通过两种方法合成，这两种方法都涉及氯化锡催化。一种方法涉及N4-酰基胞嘧啶(I)与1-O-乙酰基-2, 3, 5-三-O-苯甲酰基-β-D-呋喃核糖的缩合反应(II)，另一种方法涉及N4-酰基胞嘧啶与酰基肌苷或酰基鸟苷(IVa-d)之间的转核苷酸反应。N4-辛酰基-2', 3', 5'-三乙酰基胞苷(IIIf)通过去酰化反应高产率地转化为胞苷。
• Simple Synthesis of Some Pentafluoropropenyl Derivatives of Pyrimidine and Purine Based on Addition−Elimination Reaction
  作者：Hanna Wójtowicz-Rajchel、Michał Migas、Henryk Koroniak

  DOI：10.1021/jo061500z

  日期：2006.11.1

  pentafluoropropenyl derivatives of pyrimidine and purine bases have been obtained in good to high yield. The procedure involves the reaction of appropriate lithium derivatives prepared from both electron-rich and electron-poor pyrimidines, with the hexafluoropropene at a low temperature, via an addition−elimination process. Organolithiums of pyrimidine and purine bases give addition−elimination products as

  已经以良好至高收率获得了嘧啶和嘌呤碱的各种五氟丙烯基衍生物。该程序涉及通过加成消除法在低温下由富电子和贫电子嘧啶制备的合适的锂衍生物与六氟丙烯反应。嘧啶和嘌呤碱的有机锂以E / Z混合物形式提供加成消除产物，而受保护的肌苷的氨基酰胺锂与六氟丙烯的反应产物则含有痕量的加成产物以及稳定的全氟烯胺。所提出的方法允许快速方便地获得一系列全氟乙烯基核碱基。
• The Lipophilic Purine Nucleoside—Tdp1 Inhibitor—Enhances DNA Damage Induced by Topotecan In Vitro and Potentiates the Antitumor Effect of Topotecan In Vivo
  作者：Irina A. Chernyshova、Aleksandra L. Zakharenko、Nikolay N. Kurochkin、Nadezhda S. Dyrkheeva、Tatyana E. Kornienko、Nelly A. Popova、Valeriy P. Nikolin、Ekaterina S. Ilina、Timofey D. Zharkov、Maxim S. Kupryushkin、Vladimir E. Oslovsky、Mikhail S. Drenichev、Olga I. Lavrik

  DOI：10.3390/molecules28010323

  日期：——

  The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug. We hypothesize that Tdp1 inhibition would sensitize cells towards the effect of Tpc. Herein, we report the synthesis and study of lipophilic derivatives of purine nucleosides that efficiently suppress Tdp1 activity, with IC50 values in the 0.3–22.0 μM range. We also showed that this compound class can enhance DNA damage induced by topotecan in vitro by Comet assay on human cell lines HeLa and potentiate the antitumor effect of topotecan in vivo on a mice ascitic Krebs-2 carcinoma model. Thereby, this type of compound may be useful to develop drugs, that sensitize the effect of topotecan and reduce the required dose and, as a result, side effects.

  使用癌症化疗增敏剂是诱导临床使用的抗癌治疗效果的一种很有前景的方法。其中一个有趣的靶点是酪氨酰-DNA磷酸二酯酶1（Tdp1），它是一种DNA修复酶，可阻止拓扑异构酶1（Top1）抑制剂（如拓扑替康（Tpc））的作用。Tdp1 能消除在托泊替康作用下出现的 Top1-DNA（Top1c）共价复合物，并决定这种药物的细胞毒性作用。我们假设抑制 Tdp1 会使细胞对 Tpc 的作用敏感。在此，我们报告了亲脂性嘌呤核苷衍生物的合成和研究，它们能有效抑制 Tdp1 的活性，IC50 值在 0.3-22.0 μM 范围内。我们还发现，通过彗星试验（Comet assay）对人细胞株 HeLa 进行体外检测，这类化合物能增强托泊替康诱导的 DNA 损伤，并能增强托泊替康对小鼠腹水克雷布斯-2 癌模型的体内抗肿瘤作用。因此，这种化合物可能有助于开发药物，使托泊替康的作用更加敏感，从而减少所需剂量和副作用。

• High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries
  作者：Brett C. Bookser、Nicholas B. Raffaele

  DOI：10.1021/jo061885l

  日期：2007.1.1

  [GRAPHICS]The Vorbruggen glycosylation reaction was adapted into a one-step 5 min/130 degrees C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl triflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield +/- SD was 26 +/- 16%, and the average purity +/- SD was 95 +/- 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
• Ishido, Yoshiharu; Sakairi, Nobuo; Okazaki, Kei, Journal of the Chemical Society. Perkin transactions I, 1980, p. 563 - 573
  作者：Ishido, Yoshiharu、Sakairi, Nobuo、Okazaki, Kei、Nakazaki, Nobuo

  DOI：——

  日期：——