8-bromo-N-1-[(1R,2S,3R,4R)-2,3-(isopropylidenedioxy)-4-[[(bisphenylthiophosphoryl)oxy]methyl]cyclopentyl]-2',3'-O-isopropylideneinosine | 295805-80-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-bromo-N-1-[(1R,2S,3R,4R)-2,3-(isopropylidenedioxy)-4-[[(bisphenylthiophosphoryl)oxy]methyl]cyclopentyl]-2',3'-O-isopropylideneinosine
• 英文别名: 1-[(3aS,4R,6R,6aR)-6-[bis(phenylsulfanyl)phosphoryloxymethyl]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-9-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromopurin-6-one
• CAS: 295805-80-0
• 化学式: C₃₄H₃₈BrN₄O₉PS₂
• 分子量: 821.707
• InChiKey: ZSYBKFMSHJMVHN-HBNCQPOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  51
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  194
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  8-bromo-N-1-[(1R,2S,3R,4R)-2,3-(isopropylidenedioxy)-4-[[(bisphenylthiophosphoryl)oxy]methyl]cyclopentyl]-2',3'-O-isopropylideneinosine 在 四氮唑 、 甲酸 、 亚硝酸正戊酯 、 碘 作用下， 以 吡啶 、 乙酸酐 、 溶剂黄146 为溶剂， 反应 3.5h， 生成
  参考文献：
  名称：

  An Efficient Synthesis of Cyclic IDP- and Cyclic 8-Bromo-IDP-Carbocyclic-Riboses Using a Modified Hata Condensation Method To Form an Intramolecular Pyrophosphate Linkage as a Key Step. An Entry to a General Method for the Chemical Synthesis of Cyclic ADP-Ribose Analogues¹

  摘要：

  An efficient synthesis of cyclic IDP-carbocyclic-ribose (3! and its 8-bromo derivative 6, as stable mimics of cyclic ADP-ribose, was achieved, and a condensation reaction with phenylthiophosphate-type substrate 15 or 16 to form an intramolecular pyrophosphate linkage was a key step. N-1-Carbocyclic-ribosylinosine derivative 28 and the corresponding 8-bromo congener 24 were prepared via condensation between N-1-(2,4-dinitrophenyl)inosine derivative 17 and a known optically active carbocyclic amine 18. Compounds 24 and 28 were then converted to the corresponding 5''-phosphoryl-5'-phenylthiophosphate derivatives 15 and 16, respectively, which were substrates for the condensation reaction to form an intramolecular pyrophosphate linkage. Treatment of 8-bromo substrate 15 with It or AgNO3 in the presence of molecular sieves 3A (MS 3A) in pyridine at room temperature gave the desired cyclic product 12 quantitatively, while the yield was quite low without MS. The similar reaction of 8-unsubstituted substrate 16 gave the corresponding cyclized product 32 in 81% yield. Acidic treatment of these cyclic pyrophosphates 12 and 32 readily gave the targets 6 and 3, respectively. This result suggests that the construction of N-1-substituted hypoxanthine nucleoside structures from N-1-(2, 4-dinitrophenyl)ino sine derivatives and the intramolecular condensation by activation of the phenylthiophosphate group with I-2 or AgNO3/MS 3A combine to provide a very efficient route for the synthesis of analogues of cyclic ADP-ribose such as 3 and 6. Thus, this may be an entry to a general method for synthesizing biologically important cyclic nucleotides of this type.

  DOI：

  10.1021/jo0000877
• 作为产物：
  描述：

  5-[[(3aS,4R,6R,6aR)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]iminomethylamino]-1-[(3aR,4R,6R,6aR)-6-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2-bromo-N-(2,4-dinitrophenyl)imidazole-4-carboxamide 在 四氮唑 、 2,4,6-三异丙基苯磺酰氯 、 四丁基氟化铵 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 8-bromo-N-1-[(1R,2S,3R,4R)-2,3-(isopropylidenedioxy)-4-[[(bisphenylthiophosphoryl)oxy]methyl]cyclopentyl]-2',3'-O-isopropylideneinosine
  参考文献：
  名称：

  An Efficient Synthesis of Cyclic IDP- and Cyclic 8-Bromo-IDP-Carbocyclic-Riboses Using a Modified Hata Condensation Method To Form an Intramolecular Pyrophosphate Linkage as a Key Step. An Entry to a General Method for the Chemical Synthesis of Cyclic ADP-Ribose Analogues¹

  摘要：

  An efficient synthesis of cyclic IDP-carbocyclic-ribose (3! and its 8-bromo derivative 6, as stable mimics of cyclic ADP-ribose, was achieved, and a condensation reaction with phenylthiophosphate-type substrate 15 or 16 to form an intramolecular pyrophosphate linkage was a key step. N-1-Carbocyclic-ribosylinosine derivative 28 and the corresponding 8-bromo congener 24 were prepared via condensation between N-1-(2,4-dinitrophenyl)inosine derivative 17 and a known optically active carbocyclic amine 18. Compounds 24 and 28 were then converted to the corresponding 5''-phosphoryl-5'-phenylthiophosphate derivatives 15 and 16, respectively, which were substrates for the condensation reaction to form an intramolecular pyrophosphate linkage. Treatment of 8-bromo substrate 15 with It or AgNO3 in the presence of molecular sieves 3A (MS 3A) in pyridine at room temperature gave the desired cyclic product 12 quantitatively, while the yield was quite low without MS. The similar reaction of 8-unsubstituted substrate 16 gave the corresponding cyclized product 32 in 81% yield. Acidic treatment of these cyclic pyrophosphates 12 and 32 readily gave the targets 6 and 3, respectively. This result suggests that the construction of N-1-substituted hypoxanthine nucleoside structures from N-1-(2, 4-dinitrophenyl)ino sine derivatives and the intramolecular condensation by activation of the phenylthiophosphate group with I-2 or AgNO3/MS 3A combine to provide a very efficient route for the synthesis of analogues of cyclic ADP-ribose such as 3 and 6. Thus, this may be an entry to a general method for synthesizing biologically important cyclic nucleotides of this type.

  DOI：

  10.1021/jo0000877