2,5-difluoro-4-(2-deoxy-β-L-ribofuranosyl)-aniline | 320592-33-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,5-difluoro-4-(2-deoxy-β-L-ribofuranosyl)-aniline
• 英文别名: 2,5-difluoro-4-[1-(2-deoxy-β-L-ribofuranosyl)]aniline；(2S,3R,5S)-5-(4-amino-2,5-difluorophenyl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 320592-33-4
• 化学式: C₁₁H₁₃F₂NO₃
• 分子量: 245.226
• InChiKey: DZVUYWQWUYGOHE-VWYCJHECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75.7
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,5-difluoro-4-(2-deoxy-β-L-ribofuranosyl)-aniline 在 Tris-HCl buffer 、 recombinant human cytosolic deoxycytidine kinase 、 5’-三磷酸腺苷 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成 Phosphoric acid mono-[(2S,3R,5S)-5-(4-amino-2,5-difluoro-phenyl)-3-hydroxy-tetrahydro-furan-2-ylmethyl] ester
  参考文献：
  名称：

  Phosphorylation of Isocarbostyril‐ and Difluorophenyl‐Nucleoside Thymidine Mimics by the Human Deoxynucleoside Kinases

  摘要：

  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.

  DOI：

  10.1081/ncn-200040634
• 作为产物：
  描述：

  5-O-(p-chlorobenzoyl)-1,2-O-isopropylidene-α-L-ribofuranose 在 palladium diacetate 、 palladium on activated charcoal 咪唑 、 三苯胂 、 氢气 、 碘 、 sodium methylate 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 100.0 ℃ 、101.33 kPa 条件下， 反应 37.0h， 生成 2,5-difluoro-4-(2-deoxy-β-L-ribofuranosyl)-aniline
  参考文献：
  名称：

  Chiral Synthesis of 4-[1-(2-Deoxy-β-l-ribofuranosyl)] Derivatives of 2-Substituted 5-Fluoroaniline:  “Cytosine Replacement” Analogues of Deoxy-β-l-cytidine

  摘要：

  DOI：

  10.1021/jo000510b

文献信息

• Chiral Synthesis of 4-[1-(2-Deoxy-β-<scp>l</scp>-ribofuranosyl)] Derivatives of 2-Substituted 5-Fluoroaniline:  “Cytosine Replacement” Analogues of Deoxy-β-<scp>l</scp>-cytidine
  作者：Zhi-Xian Wang、Leonard I. Wiebe、Jan Balzarini、Erik De Clercq、Edward E. Knaus

  DOI：10.1021/jo000510b

  日期：2000.12.1
• 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.