8-methylinosine | 36113-00-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 8-methylinosine
• 英文别名: 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-methyl-1H-purin-6-one
• CAS: 36113-00-5
• 化学式: C₁₁H₁₄N₄O₅
• 分子量: 282.256
• InChiKey: MNEVXVANZIKOEH-IOSLPCCCSA-N

物化性质

• 熔点：
  228-230 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  758.7±60.0 °C(Predicted)
• 密度：
  1.96±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-methylinosine 在 磷酸三乙酯 、 水 、 三氯氧磷 作用下， 反应 1.25h， 生成 8-methylinosine 5'-monophosphate
  参考文献：
  名称：

  Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from Aplysia californica:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes

  摘要：

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.

  DOI：

  10.1021/jm060275a
• 作为产物：
  描述：

  8-methyl-2',3',5'-tris-tert-butyldimethylsilylinosine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以97%的产率得到8-methylinosine
  参考文献：
  名称：

  Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from Aplysia californica:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes

  摘要：

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.

  DOI：

  10.1021/jm060275a

文献信息

• Direct C-8 lithiation of naturally-occurring purine nucleosides. A simple method for the synthesis of 8-carbon-substituted purine nucleosides.
  作者：HIROYUKI HAYAKAWA、KAZUHIRO HARAGUCHI、HIROMICHI TANAKA、TADASHI MIYASAKA

  DOI：10.1248/cpb.35.72

  日期：——

  The sugar moiety of adenosine, inosine, or guanosine was protected with a tert-butyldimethylsilyl group. The C-8 lithiation of these protected nucleosides was carried out with lithium diisopropylamide in tetrahydrofuran at below -70°C. The reactions of the C-8-lithiated species with MeI, HCO2Me, and ClCO2Me were examined. The resulting products having a carbon substituent at the C-8 position were converted to the corresponding 8-carbon-substituted purine nucleosides by treatment with tetrabutylammonium fluoride. The whole sequence constitutes a simple method for the preparation of 8-carbon-substituted purine nucleosides from intact purine nucleosides.

  腺苷、肌苷或鸟苷的糖部分被特丁基二甲基硅基保护。对这些保护的核苷进行了C-8锂化反应，反应使用了二异丙基胺锂，在低于-70°C的四氢呋喃中进行。C-8锂化物与MeI、HCO2Me和ClCO2Me的反应进行的研究。所得到的在C-8位有碳取代基的产物经过四丁基氟铵处理后转化为相应的8-碳取代的嘌呤核苷。整个过程构成了一种从完整的嘌呤核苷制备8-碳取代嘌呤核苷的简单方法。
• Structural Determinants for N1/N7 Cyclization of Nicotinamide Hypoxanthine 5‘-Dinucleotide (NHD⁺) Derivatives by ADP-Ribosyl Cyclase from <i>Aplysia </i><i>californica</i>:  Ca²⁺-Mobilizing Activity of 8-Substituted Cyclic Inosine 5‘-Diphosphoribose Analogues in T-Lymphocytes
  作者：Christelle Moreau、Gerd K. Wagner、Karin Weber、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm060275a

  日期：2006.8.1

  A series of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) analogues modified at C-8 (2-5) and 7-deaza-NHD+ were synthesized, and cyclization in the presence of Aplysia ADP-ribosyl cyclase was studied. All 8-substituted NHD+ analogues were converted into their N1-cyclic forms by the enzyme, while in contrast, 7-deaza- NHD+ 17 was hydrolyzed into 7-deazainosine 5'-diphosphoribose (7-deaza- IDPR) 25. Correlations are made showing that the conformation of the NHD+ substrate is the key to successful cyclization. The pharmacological activities of these novel cIDPR derivatives were evaluated in both permeabilized and intact Jurkat T-lymphocytes. The results show that in permeabilized cells both 8-iodo 1g and 8-N3-N1-cIDPR 1d have an activity comparable to that of cADPR, while 8-iodo 1g and 8-phenyl-N1-cIDPR 1c have a small but significant effect in intact cells and can therefore be regarded as membrane-permeant; thus, cIDPR derivatives are emerging as important novel biological tools to study cADPR-mediated Ca2+ release in T-cells.