(+)-(2R,4S)-9-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-dioxolan-4-yl>-6-chloropurine | 145439-99-2

• 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: (+)-(2R,4S)-9-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-dioxolan-4-yl>-6-chloropurine
• 英文别名: tert-butyl-[[(2R,4S)-4-(6-chloropurin-9-yl)-1,3-dioxolan-2-yl]methoxy]-diphenylsilane
• CAS: 145439-99-2
• 化学式: C₂₅H₂₇ClN₄O₃Si
• 分子量: 495.053
• InChiKey: UBBMLRKMUZXFHZ-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.93
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-(2R,4S)-9-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-dioxolan-4-yl>-6-chloropurine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以96%的产率得到(+)-(2R,4S)-6-chloro-9-<2-(hydroxymethyl)-1,3-dioxolan-4-yl>purine
  参考文献：
  名称：

  1,3-Dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes

  摘要：

  In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 muM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine greater-than-or-equal-to adenine greater-than-or-equal-to 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine congruent-to N6-methyladenine congruent-to 6-mercaptopurine congruent-to 6-(methylthio)purine.

  DOI：

  10.1021/jm00053a004
• 作为产物：
  描述：

  6-氯嘌呤 在 ammonium sulfate 、 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 生成 (+)-(2R,4S)-9-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-dioxolan-4-yl>-6-chloropurine
  参考文献：
  名称：

  1,3-Dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes

  摘要：

  In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 muM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine greater-than-or-equal-to adenine greater-than-or-equal-to 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine congruent-to N6-methyladenine congruent-to 6-mercaptopurine congruent-to 6-(methylthio)purine.

  DOI：

  10.1021/jm00053a004

文献信息

• 1,3-Dioxolanylpurine nucleosides (2R,4R) and (2R,4S) with selective anti-HIV-1 activity in human lymphocytes
  作者：Hea O. Kim、Raymond F. Schinazi、Satyanarayana Nampalli、Kirupathevy Shanmuganathan、Deborah L. Cannon、Antonio J. Alves、Lak S. Jeong、J. Warren Beach、Chung K. Chu

  DOI：10.1021/jm00053a004

  日期：1993.1

  In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV-1 agents, various enantiomers of pure dioxolanylpurine nucleosides were synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 1, which was synthesized in nine steps from 1,6-anhydro-beta-D-mannose, was condensed with 6-chloropurine, 6-chloro-2-fluoropurine, and 2,6-dichloropurine in the presence of TMS triflate. The chloro or fluoro substituents were readily converted into amino, N-methylamino, hydroxy, methoxy, thiol, and methylthio under appropriate reaction conditions. Upon evaluation of these dioxolanes, the guanine derivative 24 exhibited the most potent anti-HIV-1 activity without cytotoxicity up to 100 muM in various cells. The decreasing antiviral activity order of beta-isomers was as follows: guanine > 6-chloro-2-aminopurine > 2-fluoroadenine greater-than-or-equal-to adenine greater-than-or-equal-to 2,6-diaminopurine > hypoxanthine > 2-chloroadenine > 6-chloropurine congruent-to N6-methyladenine congruent-to 6-mercaptopurine congruent-to 6-(methylthio)purine.