4'-hydroxymethyl-thymidine | 63861-63-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4'-hydroxymethyl-thymidine
• 英文别名: 4'-C-hydroxymethylthymidine；4'-(Hydroxymethyl)thymidin；4'-Hydroxymethylthymidin；1-[(2R,4S)-4-hydroxy-5,5-bis(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 63861-63-2
• 化学式: C₁₁H₁₆N₂O₆
• 分子量: 272.258
• InChiKey: ADFROXGIZKNJBH-JGVFFNPUSA-N

物化性质

• 密度：
  1.481±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4'-hydroxymethyl-thymidine 在 吡啶 、 咪唑 、 甲基溴化镁 、 氨 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 吡啶 、 二氯甲烷 为溶剂， 反应 173.5h， 生成 N-[(2R,3S,5R)-3-(tert-Butyl-dimethyl-silanyloxy)-2-(tert-butyl-dimethyl-silanyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl]-2,2,2-trifluoro-acetamide
  参考文献：
  名称：

  含4'- C-取代胸苷的寡脱氧核苷酸的合成与评价

  摘要：

  将4'- C-羟基甲基胸苷转化为4'- C-甲氧基甲基胸苷和4'- C-氨基甲基胸苷，通过亚磷酰胺化学将其掺入寡脱氧核苷酸中。修饰的寡核苷酸表现出优异的杂交性，并且对蛇毒磷酸二酯酶的稳定性显着提高。

  DOI：

  10.1016/0040-4039(96)01432-3
• 作为产物：
  描述：

  5’-O-(叔丁基二甲基甲硅烷基)胸苷 在 吡啶 、 sodium hydroxide 、 四丁基氟化铵 、 溶剂黄146 、 二甲基亚砜 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 22.0h， 生成 4'-hydroxymethyl-thymidine
  参考文献：
  名称：

  含4'- C-取代胸苷的寡脱氧核苷酸的合成与评价

  摘要：

  将4'- C-羟基甲基胸苷转化为4'- C-甲氧基甲基胸苷和4'- C-氨基甲基胸苷，通过亚磷酰胺化学将其掺入寡脱氧核苷酸中。修饰的寡核苷酸表现出优异的杂交性，并且对蛇毒磷酸二酯酶的稳定性显着提高。

  DOI：

  10.1016/0040-4039(96)01432-3

文献信息

• Sugar modified nucleosides and their use for synthesis of
  申请人：ICN Pharmaceuticals

  公开号：US05712378A1

  公开（公告）日：1998-01-27

  A number of modified nucleosides are disclosed composed of modified sugar moieties which contain substituents at C1 and C4 positions, or branched substituents at C3 and C5 positions of deoxyribose or ribose. Each nucleoside is converted to or properly protected and then converted to the corresponding phosphoramidites. These phosphoramidites are used to assemble oligonucleotides in which there is at least one of the forenoted nucleosides. These sugar modified oligonucleotides have the potential to be used as antisense therapies since they are expected to enhance nuclease resistance and cellular uptake while they maintain sequence-specificity and affinity to nucleic acid targets in vitro or in vivo.

  本发明揭示了一些改性核苷酸，由改性糖基组成，其中包含在脱氧核糖或核糖的C1和C4位置具有取代基，或在C3和C5位置具有分支取代基。每个核苷酸都被转化或适当保护，然后转化为相应的磷酰胺酯。这些磷酰胺酯用于组装寡核苷酸，在其中至少有一个上述核苷酸。这些糖修饰的寡核苷酸具有作为反义疗法的潜力，因为它们预计能够增强核酸酶抵抗力和细胞摄取，同时在体内或体外维持序列特异性和亲和力与核酸靶标。
• Sugar modified nucleosides
  申请人：Valeant Pharmaceuticals International

  公开号：US06743902B1

  公开（公告）日：2004-06-01

  A number of modified nucleosides are disclosed composed of modified sugar moieties which contain substituents at C1 and C4 positions, or branched substituents at C3 and C5 positions of deoxyribose or ribose. Each nucleoside is converted to or properly protected and then converted to the corresponding phosphoramidites. These phosphoramidites are used to assemble oligonucleotides in which there is at least one of the forenoted nucleosides. These sugar modified oligonucleotides have the potential to be used as antisense therapies since they are expected to enhance nuclease resistance and cellular uptake while they maintain sequence-specificity and affinity to nucleic acid targets in vitro or in vivo.

  本文披露了一些修饰过的核苷酸，由修饰过的糖基组成，其中包含在脱氧核糖或核糖的C1和C4位置，或在C3和C5位置有支链取代基。每个核苷酸都被转化或适当保护，然后转化为相应的磷酰胺酯。这些磷酰胺酯用于组装寡核苷酸，在其中至少有一个上述核苷酸。这些糖修饰的寡核苷酸具有成为反义疗法的潜力，因为预计它们将增强核酸酶的抵抗力和细胞摄取能力，同时在体外或体内保持序列特异性和亲和力与核酸靶标。
• Compositions and methods for detecting and modulating rna activity and gene expression
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP1418179A2

  公开（公告）日：2004-05-12

  Compositions and methods for modulating the activity of RNA and DNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. Reactive portions which act, alternatively, through phosphorodiester bond cleavage, through backbone sugar bond cleavage or through base modification are preferably employed. Groups which improve the pharmacodynamic and pharmacokinetic properties of the oligonucleotides are also useful in accordance with certain embodiments of this invention. Delivery of the reactive or non-reactive functionalities into the minor groove formed by the hybridization of the composition with the target RNA is also preferably accomplished. Therapeutics, diagnostics and research methods are also disclosed. Synthetic nucleosides and nucleoside fragments are also provided useful for elaboration of oligonucleotides and oligonucleotide analogs for such purposes.

  本文公开了调节 RNA 和 DNA 活性的组合物和方法。根据优选的实施方案，反义组合物由靶向部分和反应部分组成。反应部分最好通过磷酸二酯键裂解、骨架糖键裂解或碱基修饰起作用。根据本发明的某些实施方案，改善寡核苷酸药效学和药代动力学特性的基团也是有用的。最好还能将反应性或非反应性官能团输送到组合物与目标 RNA 杂交形成的次凹槽中。本发明还公开了治疗、诊断和研究方法。本发明还提供了合成核苷和核苷片段，可用于制备用于上述目的的寡核苷酸和寡核苷酸类似物。
• Branched immunomodulatory compounds and methods of using the same
  申请人：Dynavax Technologies Corporation

  公开号：US20040136948A1

  公开（公告）日：2004-07-15

  The invention provides immunomodulatory compounds and methods for immunomodulation of cells and individuals using the immunomodulatory compounds.

  本发明提供了免疫调节化合物以及使用免疫调节化合物对细胞和个体进行免疫调节的方法。
• Methods and compositions for in vitro and in vivo use of parallel stranded hairpins and triplex structures as nucleic acid ligands
  申请人：Lopez J. Martin

  公开号：US20050089893A1

  公开（公告）日：2005-04-28

  The invention sets forth parallel-stranded hairpins and parallel-stranded hairpins carrying a single strand target, the parallel-stranded hairpins containing 8-aminopurine residues and are able to bind a target molecule of interest due to specificity in the two-dimensional and three-dimensional structures of the parallel-stranded hairpins and parallel-stranded hairpins carrying a single strand target. The invention also relates to creation of a library of parallel-stranded hairpins and associated triplexes for use as aptamers, as well as methods of synthesis of parallel-stranded hairpins and use of the structures of the invention to detect and eliminate molecules of interest.

  本发明提出了平行链发蛋白和携带单链靶标的平行链发蛋白，平行链发蛋白含有 8-氨基嘌呤残基，由于平行链发蛋白和携带单链靶标的平行链发蛋白的二维和三维结构的特异性，平行链发蛋白能够结合感兴趣的靶分子。本发明还涉及平行链发针和相关三联体库的创建，以用作适配体，以及平行链发针的合成方法和使用本发明结构检测和消除感兴趣分子的方法。