1-deoxy-1-(2,4-difluorophenyl)-β-D-ribofuranose | 263701-23-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-deoxy-1-(2,4-difluorophenyl)-β-D-ribofuranose
• 英文别名: D-Ribitol, 1,4-anhydro-1-C-(2,4-difluorophenyl)-, (1S)-；(2S,3R,4S,5R)-2-(2,4-difluorophenyl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 263701-23-1
• 化学式: C₁₁H₁₂F₂O₄
• 分子量: 246.211
• InChiKey: PVOSUMDUOMMGTK-DBIOUOCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  69.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-deoxy-1-(2,4-difluorophenyl)-β-D-ribofuranose 在 吡啶 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 [(2S,3S,3aR,9aR)-2-(2,4-Difluoro-phenyl)-5,5,7,7-tetraisopropyl-tetrahydro-1,4,6,8-tetraoxa-5,7-disila-cyclopentacycloocten-3-yloxy]-acetic acid methyl ester
  参考文献：
  名称：

  The Effect of Universal Fluorinated Nucleobases on the Catalytic Activity of Ribozymes

  摘要：

  Four fluoro modified universal nucleobases have been synthesized. The universal nucleobases 1 and 2, containing a 2,4-difluorobenzene as nucleobase and a 4,6-difluorobenzimidazole, respectively, were chemically incorporated into a selected hammerhead ribozyme sequence which has already been retrovirally expressed as an anti-HIV ribozyme to investigate their effect on the catalytic activity of the ribozymes. The substitution of the natural nucleosides with either 1 or 2 results only in a small decrease of the catalytic activity. The K-m value for the monosubstituted ribozyme with a 2,4-difluorobenzene is 309 nM(-1), the corresponding k(cat) is 2.91 (.) 10(-3) min(-1). A disubstituted hammerhead ribozyme carrying one of each modification has also been synthesized. For a further stabilization of the ribozyme/substrate complex 2'-(beta-aminoethoxy) modified fluorinated nucleosides 15 and 16 have been developed.

  DOI：

  10.1081/ncn-120022962
• 作为产物：
  描述：

  2,3,5-三苄氧基-D-核糖酸-1,4-内酯 在 三乙基硅烷 、 正丁基锂 、 甲酸 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 作用下， 以 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 乙酸乙酯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 7.33h， 生成 1-deoxy-1-(2,4-difluorophenyl)-β-D-ribofuranose
  参考文献：
  名称：

  通过氟在碱基类似物中的位置控制蛋白质-RNA 复合物的稳定性

  摘要：

  描述了在参与 SL2 RNA 和 U1A 蛋白之间叠加相互作用的位置处取代的非极性碱基类似物的电子特性的修改效果。观察到与仅在单个氟原子的取代位置不同的碱基类似物形成的复合物之间的稳定性存在惊人的大差异。非极性碱基类似物和氨基酸侧链之间相互作用的高级从头计算的结果与实验观察到的复杂稳定性趋势相关，这表明由于氟的位置和程度的变化导致堆积相互作用的变化取代有助于氟取代对 U1A-SL2 RNA 复合物稳定性的影响。

  DOI：

  10.1021/ja102601h

文献信息

• Steric Effects in RNA Interference: Probing the Influence of Nucleobase Size and Shape
  作者：Alvaro Somoza、Adam P. Silverman、Rand M. Miller、Jijumon Chelliserrykattil、Eric T. Kool

  DOI：10.1002/chem.200800837

  日期：2008.9.8

  Sequence-selectivity studies were carried out at this position with mutated target mRNAs and nucleobase analogues with varied size (2,4-difluoro- and 2,4-dichlorobenzene) and different shape (2,3-dichlorobenzene, 4-methylbenzimidazole). The results point out the importance of nucleobase shape and steric effects in RNA interference.

  具有不同大小和形状的非极性核苷已被用于研究氢键稳定和空间效应对RNA干扰的影响。siRNA导链的尿嘧啶和腺嘌呤残基已被尿嘧啶和腺嘌呤的非极性等位基因以及空间变体所取代。针对海肾荧光素酶mRNA的RNAi实验表明，siRNA热稳定性与基因抑制密切相关。有趣的是，在引导链上第7位修饰的siRNA没有遵循这种相关性，尽管具有较低的热稳定性，但仍具有大量的RNAi活性。在此位置进行了具有可变大小（2,4-二氟和2,4-二氯苯）和不同形状（2,3-二氯苯，4-甲基苯并咪唑）的突变靶mRNA和核碱基类似物的序列选择性研究。
• 10.1081/ncn-200060151
  作者：Kloepffer、Engels

  DOI：10.1081/ncn-200060151

  日期：——

  The expression “universal base” is very often used to express hybridization properties and recognition patterns of nucleosides. Their behaviour in biological applications, however, is of great interest regarding, e.g., their incorporation by polymerases. The 4,6-difluorobenzimidazole and the 2,4-difluorobenzene nucleoside analogues have proven to be universal bases that do not discriminate between

  “通用碱基”一词经常用于表达核苷的杂交特性和识别模式。然而，它们在生物学应用中的行为在例如它们被聚合酶掺入方面引起了极大的兴趣。4,6-二氟苯并咪唑和 2,4-二氟苯核苷类似物已被证明是通用碱基，不能区分 RNA 双链体中的四种天然核碱基。因此，我们合成了相应的三磷酸盐来评估它们在聚合酶催化反应中的行为并研究它们作为 T7 RNA 聚合酶底物的能力。
• Synthesis of Fluorobenzene and Benzimidazole Nucleic-Acid Analogues and Their Influence on Stability of RNA Duplexes
  作者：Jörg Parsch、Joachim W. Engels

  DOI：10.1002/1522-2675(20000809)83:8<1791::aid-hlca1791>3.0.co;2-k

  日期：2000.8.9

  Six different ribonucleoside phosphoramidites with fluorobenzenes or fluorobenzimidazoles as base analogues, one abasic site, and inosine were synthesized and incorporated into oligoribonucleotides. The oligomers were investigated by means of UV and CD spectroscopy to assess the contribution of H-bonding, base stacking, and solvation to the stability of the RNA duplex. CD Spectra show that the incorporation of modified nucleosides does not lead to changes in the structure of RNA. The T-m differences determined are based on changes in base stacking and solvation. Individual contributions of base stacking and solvation of the modified nucleosides could be determined. In fluorobenzene . fluorobenzimidazole-modified base pairs, a duplex-stabilizing force was found that points to a weak F ... H H-bond.
• RNA RECOGNITION BY FLUOR-AROMATIC SUBSTITUTED
  作者：A. Zivković、J. W. Engels

  DOI：10.1081/ncn-200059755

  日期：2005.4.1

  RNA exhibits a higher structural diversity than DNA and is an important molecule in the biology of life. It shows a number of secondary structures such as duplexes, hairpin loops, bulges, internal loops, etc. However, in natural RNA, bases are limited to the four Predominant structures Q, C, A, and G and so the number of compounds that can be used for investigation of parameters of base stacking, base pairing, and hydrogen bond is limited. We synthesized different fluoromodifications of RNA building blocks: 1'-deoxy- 1'-phenyl-beta-D-ribofuranose (B), 1'-deoxy- 1'-(4-fluorophenyl)-beta-D-ribofuranose (4 FB), 1'-deoxy- 1'-(2,4-difluorophenyl)-beta-D-ribofuranose (2,4 DFB), 1'-deoxy-1'-(2,4,5-trifluorophenyl)-beta-D-ribofuranose (2,4,5 TFB), 1'-deoxy-1'-(2,4,6-trifluorophenyl)-beta-D-ribofuranose, 1'-deoxy- 1'-(pentafluorophenyl)-beta-D-ribofuranose (PFB), 1'-deoxy-1'-(benzimidazol-1-yl)-beta-D-ribofuranose (BI), 1'-deoxy-1'-(4-fluoro- 1H-benzimidazol-1-yl)-beta-D-ribofuranose (4 FBI), 1'-deoxy-1'-(6-fluoro-1H-benzimidazol-1-y1)-beta-D-ribofuranose(6FBI), 1'-deoxy-1'-(4,6-difluoro-IH-benzimidazol-1-yl)-beta-D-ribofuranose(4,6 DFBI), 1'-deoxy-1'-(4-trifluoromethyl-1H-benzimidazol-1-yl)-beta-D-ribofuranose (4 TFM), 1'-deoxy-1'-(5-trifluoromethyl-1H-benzimidazol-1-yl)-beta-D-ribofuranose (5 TFM), and 1'-deoxy-1'-(6-trifluoromethyl- 1H-benzimidazol-1-yl)-beta-D-ribofuranose (6 TFM). These amidites were incorporated and tested in a defined A, U-rich RNA sequence (12-mer, 5'-CUU UUC XUU CUU-3' paired with 3'-GAA AAG YAA GAA-5'). Ono one position was modified, marked as X and Y, respectively. UV melting profiles of those oligonucleotides were measured.
• The Roles of Hydrogen Bonding and Sterics in RNA Interference
  作者：Alvaro Somoza、Jijumon Chelliserrykattil、Eric T. Kool

  DOI：10.1002/anie.200601311

  日期：2006.7.24