5-vinyl-3',5'-di-O-acetyl-2'-deoxyuridine | 84574-82-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-vinyl-3',5'-di-O-acetyl-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-3-acetyloxy-5-(5-ethenyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate
• CAS: 84574-82-3
• 化学式: C₁₅H₁₈N₂O₇
• 分子量: 338.317
• InChiKey: NJIURYWYNYFOHY-YNEHKIRRSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-vinyl-3',5'-di-O-acetyl-2'-deoxyuridine 在 二乙胺基三氟化硫 、 一氯化碘 作用下， 以 水 、 乙腈 为溶剂， 反应 0.83h， 生成 5-(1-ethoxy-2-iodoethyl)-3',5'-di-O-acetyl-2'-deoxyuridine
  参考文献：
  名称：

  5-（1,2-二卤乙基）-2'-脱氧尿苷及相关类似物的合成及性质

  摘要：

  AbstractThe regiospecific reaction of 5‐vinyl‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (2) with HOX (X = Cl, Br, I) yielded the corresponding 5‐(1‐hydroxy‐2‐haloethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridines 3a‐c. Alternatively, reaction of 2 with iodine monochloride in aqueous acetonitrile also afforded 5‐(1‐hydroxy‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3c). Treatment of 5‐(1‐hydroxy‐2‐chloroethyl)‐ (3a) and 5‐(1‐hydroxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3b) with DAST (Et2NSF3) in methylene chloride at ‐40° gave the respective 5‐(1‐fluoro‐2‐chloroethyl)‐ (6a, 74%) and 5‐(1‐fluoro‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6b, 65%). In contrast, 5‐(1‐fluoro‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6e) could not be isolated due to its facile reaction with methanol, ethanol or water to yield the corresponding 5‐(1‐methoxy‐2‐iodoethyl)‐ (6c), 5‐(1‐ethoxy‐2‐iodoethyl)‐ (6d) and 5‐(1‐hydroxy‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3c). Treatment of 5‐(1‐hydroxy‐2‐chloroethyl)‐ (3a) and 5‐(1‐hydroxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3b) with thionyl chloride yielded the respective 5‐(1,2‐dichloroethyl)‐ (6f, 85%) and 5‐(1‐chloro‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6g, 50%), whereas a similar reaction employing the 5‐(1‐hydroxy‐2‐iodoethyl)‐ compound 3c afforded 5‐(1‐methoxy‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6c), possibly via the unstable 5‐(1‐chloro‐2‐iodoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine intermediate 6h. The 5‐(1‐bromo‐2‐chloroethyl)‐ (6i) and 5‐(1,2‐dibromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6j) could not be isolated due to their facile conversion to the corresponding 5‐(1‐ethoxy‐2‐chloroethyl)‐ (6k) and 5‐(1‐ethoxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (61). Reaction of 5‐(1‐hydroxy‐2‐bromoethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (3b) with methanolic ammonia, to remove the 3′,5′‐di‐O‐acetyl groups, gave 2,3‐dihydro‐3‐hydroxy‐5‐(2′‐deoxy‐β‐D‐ribofuranosyl)‐furano[2,3‐d]pyrimidine‐6(5H)‐one (8). In contrast, a similar reaction of 5‐(1‐fluoro‐2‐chloroethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridine (6a) yielded (E)‐5‐(2‐chlorovinyl)‐2′‐deoxyuridine (1b, 23%) and 5‐(2′‐deoxy‐β‐D‐ribofuranosyl)furano[2,3‐d]pyrimidin‐6(5H)‐one (9, 13%). The mechanisms of the substitution and elimination reactions observed for these 5‐(1,2‐dihaloethyl)‐3′,5′‐di‐O‐acetyl‐2′‐deoxyuridines are described.

  DOI：

  10.1002/jhet.5570280819

文献信息

• Synthesis of 5-(1-azidovinyl) and 5-[2-(1-azirinyl)] analogs of 2′-deoxyuridine
  作者：Rakesh Kumar、Leonard I. Wiebe、Edward E. Knaus

  DOI：10.1139/v96-178

  日期：1996.9.1

  The regiospecific addition of bromine azide to the vinyl substituent of 5-vinyl-3′,5′-di-O-acetyl- (or tert-butyldimethylsilyl)-2′-deoxyuridines (2) yielded the corresponding 5-(1-azido-2-bromoethyl)-3′,5′-di-O-protected-2′-deoxyuridines (3). Treatment of the 5-(1-azido-2-bromoethyl) compounds 3 with t-BuOK, to effect the base-catalyzed elimination of HBr, afforded the corresponding 5-(1-azidovinyl)-2′-deoxyuridines (4, 7). Thermal decomposition of 5-(1-azidovinyl)-2′-deoxyuridine (7) at 110 °C in dioxane yielded 5-[2-(1 -azirinyl)]-2′-deoxyuridine (9). 5-(1 -Azidovinyl)-2′-deoxyuridine (7) exhibited appreciable in vitro antiviral activities againist herpes simplex virus type 1 (HSV-1) and varizella zoster virus (VZV). Athough 7 increased the length of survival of HSV-1 brain-infected mice, it did not decrease the mortality rate relative to placebo. 5-[2-(1-Azirinyl)]-2′-deoxyuridine (9) was an inactive antiviral agent. Key words: azidovinyl, azirinyl, 2′-deoxyuridine, antiviral activity.

  溴化物对5-乙烯基-3′,5′-二-O-乙酰基-(或叔丁基二甲基硅基)-2′-脱氧尿苷（2）的乙烯基取代物的区域特异性加成产生相应的5-(1-叠氮基-2-溴乙基)-3′,5′-二-O-保护基-2′-脱氧尿苷（3）。用t-BuOK处理5-(1-叠氮基-2-溴乙基)化合物3，以实现碱催化的HBr消除，得到相应的5-(1-叠氮基乙烯基)-2′-脱氧尿苷（4, 7）。在二噁烷中将5-(1-叠氮基乙烯基)-2′-脱氧尿苷（7）在110°C下热分解，得到5-[2-(1-环氧基)]-2′-脱氧尿苷（9）。5-(1-叠氮基乙烯基)-2′-脱氧尿苷（7）在体外表现出对单纯疱疹病毒1型（HSV-1）和水痘-带状疱疹病毒（VZV）的可观抗病毒活性。尽管7延长了HSV-1感染小鼠的存活时间，但与安慰剂相比，未降低死亡率。5-[2-(1-环氧基)]-2′-脱氧尿苷（9）是一种无活性的抗病毒剂。关键词：叠氮基乙烯基，环氧基，2′-脱氧尿苷，抗病毒活性。