1-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)-5-ethyluracil | 311348-86-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)-5-ethyluracil
• 英文别名: 5-ethyl-1-[(2R,3R,4S,5R)-3-hydroxy-4-phenylmethoxy-5-(phenylmethoxymethyl)-5-(2-triethylsilylethynyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 311348-86-4
• 化学式: C₃₃H₄₂N₂O₆Si
• 分子量: 590.792
• InChiKey: WUWRGYIHVPTSMG-RCANGYALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)-5-ethyluracil 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以84%的产率得到1-(4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)-5-ethyluracil
  参考文献：
  名称：

  Syntheses of 4‘-C-Ethynyl-β-d-arabino- and 4‘-C-Ethynyl-2‘-deoxy-β-d-ribo-pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity

  摘要：

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.

  DOI：

  10.1021/jm000209n
• 作为产物：
  描述：

  5-乙基尿嘧啶 在 甲醇 、 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 25.0h， 生成 1-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)-5-ethyluracil
  参考文献：
  名称：

  Syntheses of 4‘-C-Ethynyl-β-d-arabino- and 4‘-C-Ethynyl-2‘-deoxy-β-d-ribo-pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity

  摘要：

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.

  DOI：

  10.1021/jm000209n

文献信息

• Syntheses of 4<i>‘</i><i>-</i><i>C</i>-Ethynyl-β-<scp>d</scp>-<i>arabino- </i>and 4‘-<i>C-</i>Ethynyl-2<i>‘</i>-deoxy-β-<scp>d</scp>-<i>ribo-</i>pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity
  作者：Hiroshi Ohrui、Satoru Kohgo、Kenji Kitano、Shinji Sakata、Eiichi Kodama、Kazuhisa Yoshimura、Masao Matsuoka、Shiro Shigeta、Hiroaki Mitsuya

  DOI：10.1021/jm000209n

  日期：2000.11.1

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.