(4R,5R)-5-{[(tert-butyldiphenylsilyl)oxy]methyl}-4-[tri(methylthio)methyl]tetrahydrofuran-2-one | 529495-75-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (4R,5R)-5-{[(tert-butyldiphenylsilyl)oxy]methyl}-4-[tri(methylthio)methyl]tetrahydrofuran-2-one
• CAS: 529495-75-8
• 化学式: C₂₅H₃₄O₃S₃Si
• 分子量: 506.827
• InChiKey: OUHGBLUDTRWKPR-YADHBBJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.24
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (4R,5R)-5-{[(tert-butyldiphenylsilyl)oxy]methyl}-4-[tri(methylthio)methyl]tetrahydrofuran-2-one 在 吡啶 、 硫酸氢铵 、 二异丁基氢化铝 、 六甲基二硅氮烷 作用下， 以 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 3.25h， 生成 1-[5'-O-tert-butyldiphenylsilyl-2',3'-dideoxy-3'-C-tris(methylthio)methyl-α-L-erythro-pentofuranosyl]-5-fluorouracil
  参考文献：
  名称：

  Research on l-Nucleosides. synthesis and biological evaluation of a series of l- and d-2′,3′-Dideoxy-3′-[tris(methylthio)methyl]-β-pentofuranosyl nucleosides

  摘要：

  Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3-tris(methylthio)methyl group allowed a good stereo selectivity level. All the compounds of both enantiomeric series showed high IC50 values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00460-1
• 作为产物：
  描述：

  三(甲基硫代)甲烷 、 (R)-(+)-5-(tert-butyldiphenylsilanyloxymethyl)-5H-furan-2-one 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 以81%的产率得到(4R,5R)-5-{[(tert-butyldiphenylsilyl)oxy]methyl}-4-[tri(methylthio)methyl]tetrahydrofuran-2-one
  参考文献：
  名称：

  Research on l-Nucleosides. synthesis and biological evaluation of a series of l- and d-2′,3′-Dideoxy-3′-[tris(methylthio)methyl]-β-pentofuranosyl nucleosides

  摘要：

  Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3-tris(methylthio)methyl group allowed a good stereo selectivity level. All the compounds of both enantiomeric series showed high IC50 values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00460-1