1-(3,5-di-O-benzyl-4-C-ethynyl-β-D-arabino-pentofuranosyl)uracil | 306305-03-3

• 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-ethynyl-β-D-arabino-pentofuranosyl)uracil
• 英文别名: 1-[(2R,3S,4S,5R)-5-ethynyl-3-hydroxy-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 306305-03-3
• 化学式: C₂₅H₂₄N₂O₆
• 分子量: 448.475
• InChiKey: QLHXOTWXEYLGTH-LYGMZBLVSA-N

物化性质

• 熔点：
  105-106 °C
• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 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-ethynyl-β-D-arabino-pentofuranosyl)uracil 在 ammonium hydroxide 、 Cl₂P(O)OC₆H₄Cl 、 三溴化硼 作用下， 以 1,4-二氧六环 、 吡啶 、 二氯甲烷 为溶剂， 生成 4'-C-ethynyl-β-D-arabino-pentofuranosyl cytosine
  参考文献：
  名称：

  Synthesis of 4′-C-Ethynyl-β-D-arabino- and 4′-C-Ethynyl-2′-deoxy-β-D-ribo- pentofuranosyl Pyrimidines, and Their Biological Evaluation

  摘要：

  4′-C-乙炔基-β-D-阿拉伯五碳呋喃糖胸腺嘧啶（14）和细胞嘧啶（16），以及4′-C-乙炔基-2′-脱氧-β-D-核糖五碳呋喃糖胸腺嘧啶（25）和细胞嘧啶（27）是通过适当保护的4′-C-羟甲基-3,5-二-O-苄基-α-D-核糖五碳呋喃糖（1）从D-葡萄糖合成的。其中，2′-脱氧衍生物25和27表现出了抗病毒活性，而胞苷衍生物16和27抑制了肿瘤细胞的生长。

  DOI：

  10.1271/bbb.63.1146
• 作为产物：
  描述：

  4-C-ethynyl-3,5-di-O-benzyl-1,2-di-O-acetyl-D-ribo-pentofuranose 在 吡啶 、 sodium hydroxide 、 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 16.0h， 生成 1-(3,5-di-O-benzyl-4-C-ethynyl-β-D-arabino-pentofuranosyl)uracil
  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