2',3',5'-tri-O-acetyl-β-arahypoxanthine | 63248-71-5

• 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-acetyl-β-arahypoxanthine
• 英文别名: [(2R,3R,4S,5R)-3,4-diacetyloxy-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 63248-71-5
• 化学式: C₁₆H₁₈N₄O₈
• 分子量: 394.341
• InChiKey: SFEQTFDQPJQUJM-YGSHXTJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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-acetyl-β-arahypoxanthine 在 diisopropylethyl amine 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 [(2R,3R,4S,5R)-3,4-diacetyloxy-5-(5-amino-4-carbamoylimidazol-1-yl)oxolan-2-yl]methyl acetate
  参考文献：
  名称：

  2,2'-脱水-阿拉伯呋喃糖基咪唑的可扩展合成

  摘要：

  我们报告了 2,2'-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide 和 2,2'-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carbonitrile 的高效和可扩展合成商业阿拉伯-腺苷。2,2'-Anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide 只需五步即可合成，只需一次色谱纯化。此外，我们报告了 2,2'-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide 向 2​​,2'-anhydro-5-amino-1-β- 的高产三步转化arabinofuranosylimidazole-4-carbonitrile。它们被认为是核糖

  DOI：

  10.1055/s-0036-1590968
• 作为产物：
  描述：

  阿糖腺苷 在 吡啶 、 水 、 adenosine deaminase 作用下， 反应 32.0h， 生成 2',3',5'-tri-O-acetyl-β-arahypoxanthine
  参考文献：
  名称：

  Synthesis, Biotransformation, and Pharmacokinetic Studies of 9-(β-d-Arabinofuranosyl)-6-azidopurine:  A Prodrug for Ara-A Designed To Utilize the Azide Reduction Pathway

  摘要：

  As a part of our efforts to design prodrugs for antiviral nucleosides, 9-(beta-4-arabinofuranosyl)-6-azidopurine (6-AAP) was synthesized as a prodrug for ara-A that utilizes the azide reduction biotransformation pathway. 6-AAP was synthesized from ara-A via its 6-chloro analogue 4. The bioconversion of the prodrug was investigated in vitro and in vivo, and the pharmacokinetic parameters were determined. For in vitro studies, 6-AAP was incubated in mouse serum and liver and brain homogenates. The half-lives of 6-AAP in serum and liver and brain homogenates were 3.73, 4.90, and 7.29 h, respectively. 6-AAP was metabolized primarily in the liver homogenate microsomal fraction by the reduction of the azido moiety to the amine, yielding ara-A. However, 6-AAP was found to be stable to adenosine deaminase in a separate in vitro study. The in vivo metabolism and disposition of ara-A and 6-AAP were conducted in mice. When 6-AAP was administered by either oral or intravenous route, the half-life of ara-A was 7-14 times higher than for ara-A administered intravenously. Ara-A could not be found in the brain after the intravenous administration of ara-A. However, after 6-AAP administration (by either oral or intravenous route), significant levels of ara-A were found in the brain. The results of this study demonstrate that 6-AAP is converted to ara-A, potentially increasing the half-life and the brain delivery of ara-A. Further studies to utilize the azide reduction approach on other clinically useful agents containing an amino group are in progress in our laboratories.

  DOI：

  10.1021/jm960339p

文献信息

• Selective Acylation of Nucleosides, Nucleotides, and Glycerol-3-phosphocholine in Water
  作者：Matthew Powner、Christian Fernández-García

  DOI：10.1055/s-0036-1588626

  日期：——

  2′,3′,5′-tri-O-acetyl-nucleosides in water has been developed. Furthermore, a long-chain selective glycerol-3-phosphocholine diacylation is elucidated. These reactions are environmentally benign, rapid, high yielding, and the products are readily purified. Importantly, this reaction may indicate a prebiotically plausible reaction pathway for the selective acylation of key metabolites to facilitate their

  2',3'-二-O-乙酰基-核苷酸-5'-磷酸、2',3'-二-O-乙酰-核苷酸-5'-三磷酸和2',3',5的方便选择性合成'-tri-O-乙酰基-核苷在水中得到了开发。此外，还阐明了长链选择性甘油-3-磷酸胆碱二酰化。这些反应对环境无害、快速、收率高，并且产物易于纯化。重要的是，该反应可能表明关键代谢物的选择性酰化以促进它们并入原代谢中的益生元似是而非的反应途径。
• Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: Palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides
  作者：Abdalla E.A. Hassan、Reham A.I. Abou-Elkhair、James M. Riordan、Paula W. Allan、William B. Parker、Rashmi Khare、William R. Waud、John A. Montgomery、John A. Secrist

  DOI：10.1016/j.ejmech.2011.10.039

  日期：2012.1

  A series of C-6 alkyl, cycloalkyl, and aryl-9-(beta-D-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia colt purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph3P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH3/MeOH gave the corresponding 6-alkyl-9-(beta-D-ribofuranosyl)purine derivatives 7-11, respectively, in good yields. Reactions of 6 with cycloalkyl(propyl, butyl, pentyl)zinc halides and aryl (phenyl, 2-thienyl)zinc halides gave under similar conditions the corresponding 6-cyclopropyl, cyclobutyl, cyclopentyl, phenyl, and thienyl -9-(beta-D-ribofuranosyl)purine derivatives 12-16, respectively in high yields. E. colt PNP showed a high tolerance to the steric and hydrophobic environment at the 6-position of the synthesized purine ribonucleosides. Significant cytotoxic activity was observed for 8, 12, 15, and 16. Evaluation of 12 and 16 against human tumor xenografts in mice did not demonstrate any selective antitumor activity. In addition, 6-methyl-9-(beta-D-arabinofuranosyl)purine (18) was prepared and evaluated. (C) 2011 Elsevier Masson SAS. All rights reserved.