1,5-anhydro-4,6-O-benzylidene-2-deoxy-3-O-methanesulfonyl-2-(thymin-1-yl)-D-altritol | 1117903-17-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: 1,5-anhydro-4,6-O-benzylidene-2-deoxy-3-O-methanesulfonyl-2-(thymin-1-yl)-D-altritol
• CAS: 1117903-17-9
• 化学式: C₁₉H₂₂N₂O₈S
• 分子量: 438.458
• InChiKey: XYLJJEDCEYFKLW-XLKGFZLASA-N

物化性质

• 密度：
  1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.24
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  125.92
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  1,5-anhydro-4,6-O-benzylidene-2-deoxy-3-O-methanesulfonyl-2-(thymin-1-yl)-D-altritol 在 吡啶 、 偶氮二异丁腈 、 氨 、 水 、 三正丁基氢锡 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 94.0h， 生成 1’,5’-anhydro-2’,3’-dideoxy-2’-[6-(dimethylamino)methylidene-5-methylisocytosin-1-yl]-6’-O-dimethoxytrityl D-arabinohexitol
  参考文献：
  名称：

  异鸟嘌呤和 5-甲基-异胞嘧啶碱基，体外和体内

  摘要：

  5-甲基异胞嘧啶 (isoC Me ) 和异鸟嘌呤 (isoG) 核苷的合成、碱基配对特性以及体外和体内特征，并入 HNA(h)（己糖醇核酸）-DNA(d) 嵌合骨架, 被描述。通过选择性脱氨作为关键步骤制备所需的 h-isoG 亚磷酰胺。正如T m测量所证明的，己糖醇对 dT 的错配辨别力稍好一些。d-isoG 碱基错配遵循 T>G>C 的顺序，而 h-isoG 碱基错配遵循 G>C>T 的顺序。h- 和 d-isoC Me碱基主要与 G 错配。酶促掺入实验表明己糖醇骨架对选择性有不同的影响。在酶促测定中，isoG 主要与 T 错误结合，isoC Me主要与 A 错误结合。进一步的体内分析证实了脱氧核糖和己糖醇 isoC Me / isoG 碱基在细胞环境中的碱基对解释模式，通过掺入碱基转化为质粒 DNA。体内结果表明，错配和错误掺入取决于碱基的骨架支架，这表明朝着正交性的合理进展。

  DOI：

  10.1002/chem.201406392
• 作为产物：
  描述：

  胸腺嘧啶 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 36.0h， 生成 1,5-anhydro-4,6-O-benzylidene-2-deoxy-3-O-methanesulfonyl-2-(thymin-1-yl)-D-altritol
  参考文献：
  名称：

  Synthesis, Improved Antisense Activity and Structural Rationale for the Divergent RNA Affinities of 3′-Fluoro Hexitol Nucleic Acid (FHNA and Ara-FHNA) Modified Oligonucleotides

  摘要：

  The synthesis, biophysical, structural, and biological properties of both isomers of 3'-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides are reported. Synthesis of the FHNA and Ara-FHNA thymine phosphoramidites was efficiently accomplished starting from known sugar precursors. Optimal RNA affinities were observed with a 3'-fluorine atom and nucleobase in a trans-diaxial orientation. The Ara-FHNA analog with an equatorial fluorine was found to be destabilizing. However, the magnitude of destabilization was sequence-dependent. Thus, the loss of stability is sharply reduced when Ara-FHNA residues were inserted at pyrimidine-purine (Py-Pu) steps compared to placement within a stretch of pyrimidines (Py-Py). Crystal structures of A-type DNA duplexes modified with either monomer provide a rationalization for the opposing stability effects and point to a steric origin of the destabilization caused by the Ara-FHNA analog. The sequence dependent effect can be explained by the formation of an internucleotide C-F center dot center dot center dot H-C pseudo hydrogen bond between F3' of Ara-FHNA and C8-H of the nucleobase from the 3'-adjacent adenosine that is absent at Py-Py steps. In animal experiments, FHNA-modified antisense oligonudeotides formulated in saline showed a potent downregulation of gene expression in liver tissue without producing hepatotoxicity. Our data establish FHNA as a useful modification for antisense therapeutics and also confirm the stabilizing influence of F(Py)center dot center dot center dot H-C(Pu) pseudo hydrogen bonds in nucleic acid structures.

  DOI：

  10.1021/ja207086x

文献信息

• TETRAHYDROPYRAN NUCLEIC ACID ANALOGS
  申请人：Swayze Eric E.

  公开号：US20090092981A1

  公开（公告）日：2009-04-09

  The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

  本公开描述了四氢吡喃核苷类似物，以及由此制备的寡聚合物化合物和使用这些寡聚合物化合物的方法。更具体地说，提供了具有一个或多个手性取代基的四氢吡喃核苷类似物，这些类似物可用于增强包括核酸酶抗性和结合亲和性在内的寡聚合物化合物的性质。在某些实施例中，本文提供的寡聚合物可以与目标RNA的部分杂交，导致目标RNA失去正常功能。