1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-β-D-ribofuranose | 304436-52-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 苯并咪唑核糖核苷和核糖核苷酸
• 英文名称: 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-β-D-ribofuranose
• 英文别名: (2R,3R,4S,5R)-2-(4,6-difluorobenzimidazol-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 304436-52-0
• 化学式: C₁₂H₁₂F₂N₂O₄
• 分子量: 286.235
• InChiKey: IIQHXKCASFGZKS-HJQYOEGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-β-D-ribofuranose 在 吡啶 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 [(2R,3R,3aR,9aR)-2-(4,6-Difluoro-benzoimidazol-1-yl)-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：

  四乙酰核糖 在 甲醇 、 N,O-双三甲硅基乙酰胺 、 氨 作用下， 以 乙腈 为溶剂， 反应 22.75h， 生成 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-β-D-ribofuranose
  参考文献：
  名称：

  Synthesis of Fluorobenzene and Benzimidazole Nucleic-Acid Analogues and Their Influence on Stability of RNA Duplexes

  摘要：

  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.

  DOI：

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

文献信息

• Chemoenzymatic Synthesis and Antiherpes Activity of 5-Substituted 4,6-Difluorobenzimidazoles Ribo- and 2′-Deoxyribonucleosides
  作者：Maria Kharitonova、Ilja Fateev、Alexei Kayushin、Irina Konstantinova、Svetlana Kotovskaya、Valeria Andronova、Georgii Galegov、Valery Charushin、Anatoly Miroshnikov

  DOI：10.1055/s-0035-1560911

  日期：——

  pyrrolidino-) in the 5-position of the benzene ring, have been synthesized. All these compounds proved to be substrates for recombinant E. coli purine nucleoside phosphorylase (PNP) in the transglycosylation reaction. Effective methods for the synthesis of ribo- and 2′-deoxyribonucleosides with high yields (60–90%) have been described, and the formation of regioisomeric N3-nucleosides of benzimidazoles have

  摘要 较早获得的一系列5,6-二取代苯并咪唑核苷在较低的体外细胞毒性下未显示任何显着的抗病毒活性。在我们的研究过程中，我们成功地将额外的氟原子引入苯并咪唑环系统。合成了一系列新的4,6-二氟苯并咪唑，在苯环的5-位带有多个基团（氟，甲氧基，乙氧基，吗啉代和吡咯烷基）。所有这些化合物被证明是转糖基化反应中重组大肠杆菌嘌呤核苷磷酸化酶（PNP）的底物。已经描述了高产率（60-90％）合成核糖-和2'-脱氧核糖核苷的有效方法，并形成了区域异构N已检测到苯并咪唑的3-核苷。阐明了针对1型单纯疱疹病毒（HSV-1）获得的核苷的生物活性。所有化合物在细胞培养Vero E6中均显示出低细胞毒性。4,5,6-三氟-1-（β- d-呋喃核糖基）苯并咪唑和5-甲氧基-4,6-二氟-1-（β- d -2'-脱氧核糖呋喃糖基）苯并咪唑被证明完全抑制了其发展。感染复数（MOI）为0.01 PFU /细胞时，病毒的细胞病变效应（CPE）。
• 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。
• 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.
• A novel entry to 2′-O-aminopropyl modified nucleosides amenable for further modifications
  作者：Jens Haas、Joachim W. Engels

  DOI：10.1016/j.tetlet.2007.10.053

  日期：2007.12

  2'-O-aminopropyl modified 4,6-difluoro-substituted benzimidazole nucleosides were synthesized in a two-step synthesis via Michael reaction and a Raney-nickel catalyzed reduction in high yields. These building blocks were used as a starting point for the conjugation of different carboxylic acids to enhance the lipophilicity or cationic character of oligonucleotides when used in biological assays or medical applications. (C) 2007 Elsevier Ltd. All rights reserved.
• 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.