5-(1,2-dichloroethyl)-3',5'-di-O-acetyl-2'-deoxyuridine | 139546-09-1

• 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-(1,2-dichloroethyl)-3',5'-di-O-acetyl-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-3-acetyloxy-5-[5-(1,2-dichloroethyl)-2,4-dioxopyrimidin-1-yl]oxolan-2-yl]methyl acetate
• CAS: 139546-09-1；139546-20-6
• 化学式: C₁₅H₁₈Cl₂N₂O₇
• 分子量: 409.223
• InChiKey: SEYVZILWMXYALU-FJAVPRTDSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-(1-hydroxy-2-chloroethyl)-3',5'-di-O-acetyl-2'-deoxyuridine 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 30.0h， 以85%的产率得到5-(1,2-dichloroethyl)-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