4-acetamido-7-fluoro-1-(2,3,5-tri-O-tert-butyldimethylsilyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridine | 247024-46-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑[4，5-c]吡啶核糖核苷和核糖核苷酸
• 英文名称: 4-acetamido-7-fluoro-1-(2,3,5-tri-O-tert-butyldimethylsilyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridine
• 英文别名: N-[1-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-7-fluoroimidazo[4,5-c]pyridin-4-yl]acetamide
• CAS: 247024-46-0
• 化学式: C₃₁H₅₇FN₄O₅Si₃
• 分子量: 669.072
• InChiKey: IOBCIRMOHBEHGY-WKZNCHQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.23
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  96.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-acetamido-7-fluoro-1-(2,3,5-tri-O-tert-butyldimethylsilyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridine 在 甲醇 、 四丁基氟化铵 、 氨 作用下， 以 四氢呋喃 为溶剂， 反应 21.5h， 生成 4-amino-7-fluoro-1-(β-D-ribofuranosyl)imidazo[4,5-c]pyridine
  参考文献：
  名称：

  Nucleosides and Nucleotides. 184. Synthesis and Conformational Investigation of Anti-Fixed 3-Deaza-3-halopurine Ribonucleosides^1,2

  摘要：

  A versatile synthetic route to 3-deaza-3-haloinosines 6-8 and 46, -adenosines 15-17 and 64, and -guanosines 25, 26, and 52 is described. 3-Deaza-3-chloro-, -bromo-, and -iodopurine ribonucleosides can be synthesized by treating the 3-deazapurine ribonucleosides with N-halosuccinimides. For the synthesis of 3-deaza-3-fluoropurine ribonucleosides, 5-formylimidazole-4-carboxamide ribosides 34 and 35 prepared from 5-iodoimidazole-4-carboxamide derivatives 29 and 31 were us ed as the key intermediates. The reaction of 34 and 35 with lithium (trimethylsilyl)acetylide and sodium cyanide, respectively, followed by appropriate manipulations gave 3-deaza-3-fluoroinosine derivative 46 and 3-deaza-3-fluoroguanosine derivative 52. 3-Deaza-3-fluoroadenosine (64) was also synthesized by selective reductive deamination of 4,6-diamino-7-fluoroimidazo[4,5-c]pyridine derivative 51, followed by deprotection. A conformational analysis using H-1 NMR and NOE experiments showed that the introduction of halogens (chloro, bromo, and iodo) into the 3-position of 3-deazapurine ribonucleosides forced fixation of the glycosyl torsion angle in the anti region, but did not-abnormally influence sugar puckering. On the other hand, 3-deaza-3-fluoropurine ribonucleosides should rotate freely around the glycosyl bond.

  DOI：

  10.1021/jo990638x
• 作为产物：
  描述：

  5-iodo-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide 在 二(氰基苯)二氯化钯 吡啶 、 咪唑 、 甲醇 、 四氧化锇 、 乙醇 、 二乙胺基三氟化硫 、 氨 、 碳酸氢钠 、 N-甲基吗啉氧化物 、 三乙胺 、 三氯氧磷 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 、 叔丁醇 为溶剂， 反应 189.08h， 生成 4-acetamido-7-fluoro-1-(2,3,5-tri-O-tert-butyldimethylsilyl-β-D-ribofuranosyl)imidazo[4,5-c]pyridine
  参考文献：
  名称：

  Nucleosides and Nucleotides. 184. Synthesis and Conformational Investigation of Anti-Fixed 3-Deaza-3-halopurine Ribonucleosides^1,2

  摘要：

  A versatile synthetic route to 3-deaza-3-haloinosines 6-8 and 46, -adenosines 15-17 and 64, and -guanosines 25, 26, and 52 is described. 3-Deaza-3-chloro-, -bromo-, and -iodopurine ribonucleosides can be synthesized by treating the 3-deazapurine ribonucleosides with N-halosuccinimides. For the synthesis of 3-deaza-3-fluoropurine ribonucleosides, 5-formylimidazole-4-carboxamide ribosides 34 and 35 prepared from 5-iodoimidazole-4-carboxamide derivatives 29 and 31 were us ed as the key intermediates. The reaction of 34 and 35 with lithium (trimethylsilyl)acetylide and sodium cyanide, respectively, followed by appropriate manipulations gave 3-deaza-3-fluoroinosine derivative 46 and 3-deaza-3-fluoroguanosine derivative 52. 3-Deaza-3-fluoroadenosine (64) was also synthesized by selective reductive deamination of 4,6-diamino-7-fluoroimidazo[4,5-c]pyridine derivative 51, followed by deprotection. A conformational analysis using H-1 NMR and NOE experiments showed that the introduction of halogens (chloro, bromo, and iodo) into the 3-position of 3-deazapurine ribonucleosides forced fixation of the glycosyl torsion angle in the anti region, but did not-abnormally influence sugar puckering. On the other hand, 3-deaza-3-fluoropurine ribonucleosides should rotate freely around the glycosyl bond.

  DOI：

  10.1021/jo990638x

文献信息

• Nucleosides and Nucleotides. 184. Synthesis and Conformational Investigation of Anti-Fixed 3-Deaza-3-halopurine Ribonucleosides¹^,²
  作者：Noriaki Minakawa、Naoshi Kojima、Akira Matsuda

  DOI：10.1021/jo990638x

  日期：1999.9.1

  A versatile synthetic route to 3-deaza-3-haloinosines 6-8 and 46, -adenosines 15-17 and 64, and -guanosines 25, 26, and 52 is described. 3-Deaza-3-chloro-, -bromo-, and -iodopurine ribonucleosides can be synthesized by treating the 3-deazapurine ribonucleosides with N-halosuccinimides. For the synthesis of 3-deaza-3-fluoropurine ribonucleosides, 5-formylimidazole-4-carboxamide ribosides 34 and 35 prepared from 5-iodoimidazole-4-carboxamide derivatives 29 and 31 were us ed as the key intermediates. The reaction of 34 and 35 with lithium (trimethylsilyl)acetylide and sodium cyanide, respectively, followed by appropriate manipulations gave 3-deaza-3-fluoroinosine derivative 46 and 3-deaza-3-fluoroguanosine derivative 52. 3-Deaza-3-fluoroadenosine (64) was also synthesized by selective reductive deamination of 4,6-diamino-7-fluoroimidazo[4,5-c]pyridine derivative 51, followed by deprotection. A conformational analysis using H-1 NMR and NOE experiments showed that the introduction of halogens (chloro, bromo, and iodo) into the 3-position of 3-deazapurine ribonucleosides forced fixation of the glycosyl torsion angle in the anti region, but did not-abnormally influence sugar puckering. On the other hand, 3-deaza-3-fluoropurine ribonucleosides should rotate freely around the glycosyl bond.