diisopropyl (E)-2-[2-(adenin-9-yl)ethylidene]-1-cyclopropylphosphonate | 883110-67-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: diisopropyl (E)-2-[2-(adenin-9-yl)ethylidene]-1-cyclopropylphosphonate
• CAS: 883110-67-6
• 化学式: C₁₆H₂₄N₅O₃P
• 分子量: 365.372
• InChiKey: VXUBFFXHLXVNRW-LFYBBSHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.15
• 重原子数：
  25.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  105.15
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  diisopropyl (E)-2-[2-(adenin-9-yl)ethylidene]-1-cyclopropylphosphonate 在 盐酸 作用下， 反应 0.33h， 以71%的产率得到{2-[2-(6-Amino-purin-9-yl)-eth-(E)-ylidene]-cyclopropyl}-phosphonic acid
  参考文献：
  名称：

  Synthesis of methylenecyclopropane analogues of antiviral nucleoside phosphonates

  摘要：

  Synthesis of methylenecyclopropane analogues of nucleoside phosphonates 6a, 6b, 7a and 7b is described. Cyclopropyl phosphonate 8 was transformed in four steps to methylenecyclopropane phosphonate 16. The latter intermediate was converted in seven steps to the key Z- and E-methylenecyclopropane alcohols 23 and 24 separated by chromatography. Selenoxide eliminations (15 -> 16 and 22 -> 23 + 24) were instrumental in the synthesis. The Z- and E-isomers 23 and 24 were transformed to bromides 25a and 25b, which were used for alkylation of adenine and 2-amino-6-chloropurine to give intermediates 26a, 26b, 26c and 26d. Acid hydrolysis provided the adenine and guanine analogues 6a, 6b, 7a and 7b. Phosphonates 6b and 7b are potent inhibitors of replication of Epstein-Barr virus (EBV). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.12.035
• 作为产物：
  描述：

  甲基磷酸二异丙酯 在 吡啶 、 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 锂硼氢 、 正丁基锂 、 四溴化碳 、 四丁基氟化铵 、 双氧水 、 溴 、 potassium carbonate 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 255.42h， 生成 diisopropyl (E)-2-[2-(adenin-9-yl)ethylidene]-1-cyclopropylphosphonate
  参考文献：
  名称：

  Synthesis of methylenecyclopropane analogues of antiviral nucleoside phosphonates

  摘要：

  Synthesis of methylenecyclopropane analogues of nucleoside phosphonates 6a, 6b, 7a and 7b is described. Cyclopropyl phosphonate 8 was transformed in four steps to methylenecyclopropane phosphonate 16. The latter intermediate was converted in seven steps to the key Z- and E-methylenecyclopropane alcohols 23 and 24 separated by chromatography. Selenoxide eliminations (15 -> 16 and 22 -> 23 + 24) were instrumental in the synthesis. The Z- and E-isomers 23 and 24 were transformed to bromides 25a and 25b, which were used for alkylation of adenine and 2-amino-6-chloropurine to give intermediates 26a, 26b, 26c and 26d. Acid hydrolysis provided the adenine and guanine analogues 6a, 6b, 7a and 7b. Phosphonates 6b and 7b are potent inhibitors of replication of Epstein-Barr virus (EBV). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.12.035

文献信息

• Synthesis of methylenecyclopropane analogues of antiviral nucleoside phosphonates
  作者：Zhaohua Yan、Shaoman Zhou、Earl R. Kern、Jiri Zemlicka

  DOI：10.1016/j.tet.2005.12.035

  日期：2006.3

  Synthesis of methylenecyclopropane analogues of nucleoside phosphonates 6a, 6b, 7a and 7b is described. Cyclopropyl phosphonate 8 was transformed in four steps to methylenecyclopropane phosphonate 16. The latter intermediate was converted in seven steps to the key Z- and E-methylenecyclopropane alcohols 23 and 24 separated by chromatography. Selenoxide eliminations (15 -> 16 and 22 -> 23 + 24) were instrumental in the synthesis. The Z- and E-isomers 23 and 24 were transformed to bromides 25a and 25b, which were used for alkylation of adenine and 2-amino-6-chloropurine to give intermediates 26a, 26b, 26c and 26d. Acid hydrolysis provided the adenine and guanine analogues 6a, 6b, 7a and 7b. Phosphonates 6b and 7b are potent inhibitors of replication of Epstein-Barr virus (EBV). (c) 2005 Elsevier Ltd. All rights reserved.