2-bromo-5,6-dichloro-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)benzimidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-bromo-5,6-dichloro-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)benzimidazole
• 英文别名: (2R,3R,4R,5R)-5-(2-bromo-5,6-dichlorobenzimidazol-1-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• 化学式: C₁₂H₁₀BrCl₂FN₂O₃
• 分子量: 400.031
• InChiKey: WEYPXLMGPUDYTO-GWOFURMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 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：
  67.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2'-氟-2'-脱氧尿苷 在 吡啶 、 citrate buffer 、 N-溴代丁二酰亚胺(NBS) 、 N-deoxyribofuranosyl transferase 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 18.17h， 生成 2-bromo-5,6-dichloro-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  Synthesis of Fluorosugar Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole as Antivirals with Potentially Increased Glycosidic Bond Stability

  摘要：

  The metabolic instability in vivo of the glycosidic bond of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) prompted us to design and synthesize the hitherto unreported fluorinated benzimidazole nucleosides 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole, 2,5,6-trichloro-1-(3-deoxy-3-fluoro-beta-D-ribofuranosyl)benzimidazole, and 2-bromo-5,6-dichloro-1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)benzimidazole. TCRB was converted into the 2',5'-ditrityl and 3'5'-dinitryl derivatives, which were fluorinated with DAST and deprotected to yield 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) and 2,5,6-trichloro-1(3-deoxy-3-fluoro-beta-D-xylofuranosyl)benzimidazole. The resulting low over yield (5%) of 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole encouraged us to develop an alternative route. The heterocycle 2,5,6-trichlorobenzimidazole was condensed with 1-bromo-3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose to give, after deprotection, 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole in a 50% overall yield. The 2'-deoxy-2'-fluoro-beta-D-ribofuranosyl compounds were prepared using 2'-deoxy-2'-fluorouridine, N-deoxyribofuranosyl transferase, and 5,6-dichlorobenzimidazole. Functionalization of the C2 position then gave the desired derivatives. Antiviral and cytotoxicity testing revealed that the deoxy fluoro arabinofuranosyl, xylofuranosyl, and ribofuranosyl derivatives were less active against human cytomegalovirus and more cytotoxic than TCRB.

  DOI：

  10.1021/jm990219s

文献信息

• US5840743A
  申请人：——

  公开号：US5840743A

  公开（公告）日：1998-11-24