1',2'-dideoxy-β-1'-(2,4-difluoro-5-methylphenyl)-D-ribofuranose | 159277-44-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1',2'-dideoxy-β-1'-(2,4-difluoro-5-methylphenyl)-D-ribofuranose
• 英文别名: 1',2'-dideoxy-1'-(2,4-difluoro-5-methylphenyl)-β-D-ribofuranose；5-(2'-deoxy-β-D-ribofuranosyl)-2,4-difluorotoluene；5-(2-deoxy-β-D-ribofuranosyl)-2,4-difluorotoluene；(2R,3S,5R)-5-(2,4-difluoro-5-methyl-phenyl)-2-(hydroxymethyl)tetrahydrofuran-3-ol；(2R,3S,5R)-5-(2,4-difluoro-5-methylphenyl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 159277-44-8
• 化学式: C₁₂H₁₄F₂O₃
• 分子量: 244.238
• InChiKey: VZSIWTWOIQVYAZ-QJPTWQEYSA-N

物化性质

• 沸点：
  364.5±42.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1',2'-dideoxy-β-1'-(2,4-difluoro-5-methylphenyl)-D-ribofuranose 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 反应 4.0h， 生成 1'-(2,4-difluorotolyl)-5'-O-(4,4'-dimethoxytrityl)-3'-O-succinyl-β-D-ribofuranose
  参考文献：
  名称：

  DNA 中的疏水性、非氢键碱基和碱基对

  摘要：

  我们报告了合成 DNA 双链体中嘧啶和嘌呤的疏水等排体的特性。苯基核苷 1 和 2 是天然胸苷核苷的非极性等排体，吲哚核苷 3 是互补嘌呤 2-氨基脱氧腺苷的类似物。核苷被掺入合成的寡脱氧核苷酸中，并相互配对并与天然碱基配对。热变性实验用于测量双链体在中性 pH 值下的稳定性。发现疏水性碱基类似物在与四种天然碱基配对时是非选择性的，但对彼此配对而不是与天然碱基配对时具有选择性。例如，化合物 2 选择性地与其自身配对，而不是与 A、T、G 或 C；发现这种选择性的大小为 6.5-9.3 °C，Tm 或 1.5-1。8 kcal/mol 的自由能 (25 °C)。检查了所有可能的疏水配对组合 1、2 和 3。结果显示配对亲和力取决于配对的性质和双链体中的位置。发现最高亲和力对是 1-1 和 2-2 自对和 1-2 杂对。当线对放置在双工的末端而不是内部时，稳定性最佳；不完美的空间模拟可能会破坏

  DOI：

  10.1021/ja00112a001
• 作为产物：
  描述：

  5-溴-2,4-二氟甲苯 在 碘 、 sodium methylate 、 magnesium 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 1',2'-dideoxy-β-1'-(2,4-difluoro-5-methylphenyl)-D-ribofuranose
  参考文献：
  名称：

  芳香非极性核苷作为嘧啶和嘌呤核苷的疏水等排体。

  摘要：

  描述了三种非极性核苷等排体的设计、合成和结构，用作 DNA 中非共价键的探针和设计的核酸结构中天然核苷的等排置换。取代的芳基格氏与 3',5'-双-O-甲苯酰-α-脱氧呋喃异戊酰氯反应，随后用甲醇钠在甲醇中脱保护，得到两个 β-C-核苷嘧啶类似物 1 和 2。二甲基吲哚基核苷 3，a嘌呤等排体是通过 4,6-二甲基吲哚的钠盐对 α-氯代脱氧呋喃核糖进行亲核置换，然后去保护而获得的。产物的区域和立体化学通过 NOE 差异光谱和 (1) H NMR 分裂模式建立。类似物 1 和 2 是胸苷的非极性等排体，核苷 3 是 2-氨基脱氧腺苷的等排体，它是胸苷的三重键沃森-克里克搭档。进行了半经验 AM1 计算以提供键长信息，以评估等排体与其天然对应物之间的结构相似性。

  DOI：

  10.1021/jo00103a013

文献信息

• SYNTHESIS OF 1-(2-DEOXY-β-<scp>D</scp>- RIBOFURANOSYL)-2,4-DIFLUORO-5-SUBSTITUTED-BENZENE THYMIDINE MIMICS,^*SOME RELATED α-ANOMERS, AND THEIR EVALUATION AS ANTIVIRAL AND ANTICANCER AGENTS
  作者：Zhi-Xian Wang、Weili Duan、Leonard I. Wiebe、Jan Balzarini、Erik De Clercq、Edward E. Knaus

  DOI：10.1081/ncn-100001435

  日期：2001.2.26

  Me, F, Cl, Br, I, CF3, CN, NO2, NH2), designed as thymidine mimics, were synthesized for evaluation as anticancer and antiviral agents. The coupling reaction of 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-α-D-ribofuranosyl chloride with an organocadmium reagent [(2,4-difluorophenyl)2Cd] afforded a mixture of the α- and β-anomeric products (α:β = 3:1 to 10:1 ratio). Treatment of the α-anomer with BF3·Et2O in

  一组具有各种C-5取代基（H，Me，F，Cl，Br，I，CF3，CN，NO2，合成了设计为胸苷模拟物的NH2）作为抗癌药和抗病毒药进行评估。3,5-双-O-（对氯苯甲酰基）-2-脱氧-α-D-呋喃呋喃糖基氯与有机镉试剂[（2,4-二氟苯基）2Cd]的偶联反应得到α-和-C的混合物β-异头物产物（α：β= 3：1至10：1的比例）。作为在主要的α-端基异构体上异构化成所需的β-端基异构体的有效方法，人们开发了在BF-​​110-C中在硝基乙烷中用BF3·Et2O处理α-端基异构体的方法。相对于胸腺嘧啶（CC50 = 10-3-10），在MTT分析（CC50 = 10−3–10−4 M范围）中，5取代的（H，Me，Cl，I，NH2）β-异头物显示出可忽略的细胞毒性。 -5 M范围），针对各种癌细胞系。相比之下，5-NO2衍生物具有更高的细胞毒性（CC50 = 10-5-6-10 M范围）。使用
• Naphthalene, Phenanthrene, and Pyrene as DNA Base Analogues:  Synthesis, Structure, and Fluorescence in DNA
  作者：Rex X.-F. Ren、Narayan C. Chaudhuri、Pamela L. Paris、Rumney、Eric T. Kool

  DOI：10.1021/ja9612763

  日期：1996.1.1

  efficient method has also been developed for epimerization of the α-anomers to β-anomers by acid-catalyzed equilibration; this isomerization is successfully carried out on the four polycyclic nucleosides as well as two substituted phenyl nucleosides. The geometry of the anomeric substitution is derived from (1)H NOE experiments and is also correlated with a single-crystal X-ray structure of one α-isomer

  我们描述了携带多环芳烃的脱氧核糖核苷的合成、结构和 DNA 掺入作为 DNA“基础”类似物。新的多环化合物是 1-萘基、2-萘基、9-菲基和 1-芘基脱氧核苷。这些化合物是使用最近开发的 C-糖苷键形成方法合成的，该方法涉及芳香族化合物的有机镉衍生物与 1α-氯代脱氧核糖前体偶联。这种偶联的主要产物是脱氧核糖苷的 α-端基异构体。还开发了一种通过酸催化平衡将 α-端基异构体差向异构化为 β-端基异构体的有效方法；这种异构化成功地对四个多环核苷以及两个取代的苯基核苷进行。异头取代的几何形状源自 (1)H NOE 实验，并且还与一种 α-异构体的单晶 X 射线结构相关。三种多环 C-核苷衍生物通过其亚磷酰胺衍生物整合到 DNA 寡核苷酸中；芘基和菲基衍生物在 DNA 序列中显示出荧光。结果 (1) 拓宽了我们的 C-糖苷偶联反应的范围，(2) 证明（使用新的酸催化差向异构化）α-和 β-异头物
• A Set of Nonpolar Thymidine Nucleoside Analogues with Gradually Increasing Size
  作者：Tae Woo Kim、Eric T. Kool

  DOI：10.1021/ol048487u

  日期：2004.10.1

  [GRAPHICS]We describe a series of nonpolar nucleoside analogues having similar shapes and gradually increasing size. The structure of the nucleobase thymine was mimicked with toluene derivatives, replacing O2/O4 with hydrogen, fluorine, chlorine, bromine, and iodine. Glycosidic bonds were formed by reactions of lithiated 2,4-dihalotoluenes with a deoxyribonolactone derivative. Structural analysis by NMR showed similar conformations across the series. The compounds are useful for study of the biological recognition of nucleotides and nucleic acids.
• Phosphorylation of Isocarbostyril‐ and Difluorophenyl‐Nucleoside Thymidine Mimics by the Human Deoxynucleoside Kinases
  作者：Ashraf Said Al‐Madhoun、Staffan Eriksson、Zhi‐Xian Wang、Ebrahim Naimi、Edward E. Knaus、Leonard I. Wiebe

  DOI：10.1081/ncn-200040634

  日期：2004.1.12

  The thymidine mimics isocarbostyril nucleosides and difluorophenyl nucleosides were tested as deoxynucleoside kinase substrates using recombinant human cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK), and mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK). The isocarbostyril nucleoside compound 1-(2-deoxy-beta-D-ribofuranosyl)-isocarbostyril (EN1) was a poor substrate with all the enzymes. The phosphorylation rates of EN1 with TKI and TK2 were <1% relative to Thd, where as the phosphorylation rates for EN1 were 1.4% and 1.1% with dCK and dGK relative to dCyd and dGuo, respectively. The analogue 1-(2-deoxy-beta-D-ribofuranosyl)-7-iodoisocarbostyril (EN2) showed poor relative-phosphorylation efficiencies (k(cat)/Kappa(m).) with both TK1 and dGK, but not with TK2. The k(cat)/Kappa(m) value for EN2 with TK2 was 12.6% relative to that for Thd. Of the difluorophenyl nucleosides, 5-(1'-(2'-deoxy-beta-D-ribofuranosyl))-2,4-difluorotoluene (JW1) and 1-(1'-(2'-deoxy-beta-D-ribofuranosyl))-2,4-difluoro-5-iodobenzene (JW2) were substrates for TK1 with phosphorylation efficiencies of about 5% relative to that for Thd. Both analogues were considerably more efficient substrates for TK2, with k(cat)/Kappa(m). values of 45% relative to that for Thd. 2,5-Difluoro-4-[1-(2-deoxy-beta-L-ribofuranosyl)]-aniline (JW5), a L-nucleoside mimic, was phosphorylated up to 15% as efficiently as deoxycytidine by dCK. These data provide a possible explanation for the previously reported lack of cytotoxicity of the isocarbostyril- and difluorophenyl nucleosides, but potential mitochondrial effects of EN2, JW1 and JW2 should be further investigated.
• Jarchow-Choy, Sarah K.; Sjuvarsson, Elena; Sintim, Herman O., Journal of the American Chemical Society, 2009, vol. 131, p. 5488 - 5494
  作者：Jarchow-Choy, Sarah K.、Sjuvarsson, Elena、Sintim, Herman O.、Eriksson, Staffan、Kool, Eric T.

  DOI：——

  日期：——