methyl 5-deoxy-5-chloro-D-ribofuranoside | 151378-77-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-deoxy-5-chloro-D-ribofuranoside
• 英文别名: 1-O-methyl-5-deoxy-5-chloro-D-ribofuranose；(2S,3S,4R)-2-(chloromethyl)-5-methoxyoxolane-3,4-diol
• CAS: 151378-77-7
• 化学式: C₆H₁₁ClO₄
• 分子量: 182.604
• InChiKey: WLLWQFXHKHNJBU-JDJSBBGDSA-N

物化性质

• 沸点：
  327.8±42.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  58.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 5-deoxy-5-chloro-D-ribofuranoside 在 吡啶 、 ammonium hydroxide 、 叠氮化锂 、 三氟化硼乙醚 、 sodium methylate 、 三苯基膦 作用下， 以 甲醇 、 硝基甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.75h， 生成 4-amino-3-iodo-1-(5-deoxy-5-amino-β-D-ribofuranosyl)pyrazolo<3,4-d>pyrimidine
  参考文献：
  名称：

  New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation

  摘要：

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

  DOI：

  10.1021/jm00074a024
• 作为产物：
  描述：

  methyl 5-deoxy-5-chloro-2,3-O-sulfinyl-D-ribofuranoside 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以81%的产率得到methyl 5-deoxy-5-chloro-D-ribofuranoside
  参考文献：
  名称：

  New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation

  摘要：

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

  DOI：

  10.1021/jm00074a024
• 作为试剂：
  描述：

  α,β-1-甲基-D-呋喃核糖苷 、 乙腈 、 三乙胺 、 氯化亚砜 在 三乙胺盐酸盐 、 乙酸乙酯 、 ammonium hydroxide 、 methyl 5-deoxy-5-chloro-D-ribofuranoside 、 ice 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以Thus, 1-O-methyl-5-deoxy-5-chloro-β-D-ribofuranose (65 g; purity: 100%; yield: 53%) was obtained的产率得到Methyl-5-chloro-5-deoxy-β-D-ribofuranosid
  参考文献：
  名称：

  PROCESS FOR PRODUCTION OF RIBOFURANOSE DERIVATIVES

  摘要：

  本发明的目的是以适合工业生产的方式提供生产1,2,3-三-O-乙酰-5-去氧核糖的方法。本发明提供了一种生产1,2,3-三-O-乙酰-5-去氧核糖的方法，该方法包括在金属催化剂存在下，对式（1）或式（2）所表示的化合物进行氢化：其中P1和P2分别表示氢原子或酰基，OP1和OP2可以结合形成缩醛基团，R表示氢原子、烷基、芳基、芳烷基或酰基；其中X1表示Br或I，P3和P4分别表示氢原子或酰基，R表示氢原子、烷基、芳基、芳烷基或酰基。

  公开号：

  US20100298550A1