8-chloro-2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine | 116285-75-7

• 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-chloro-2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine
• 英文别名: 8-chloro-2',3',5'-tris-tert-butyldimethylsilylinosine；9-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-8-chloro-1H-purin-6-one
• CAS: 116285-75-7
• 化学式: C₂₈H₅₃ClN₄O₅Si₃
• 分子量: 645.462
• InChiKey: XJDWCKBNBLSICI-UMCMBGNQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.89
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  96.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-chloro-2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以77%的产率得到8-chloroinosine
  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：

  2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine 在 lithium diisopropyl amide 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以73%的产率得到8-chloro-2',3',5'-tris-O-(tert-butyldimethylsilyl)inosine
  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

• Microwave-Assisted Direct Amination: Rapid Access to Multi-Functionalized N6-Substituted Adenosines
  作者：Trent D. Ashton、Peter J. Scammells

  DOI：10.1071/ch07340

  日期：——

  Analogues of adenosine have a range of interesting biological activities and potential therapeutic applications. A method for the efficient preparation of highly functionalized N6-substituted adenosines has been developed from the corresponding tert-butyldimethylsilyl-protected inosine. The key step in this procedure is a microwave-assisted amination reaction between an appropriately substituted inosine and an amine in the presence of PyBroP. High yields of desired N6-substituted adenosines were achieved with hindered amines and the reaction was also found to accommodate a range of substituents on the inosine precursor.

  腺苷的类似物具有一系列有趣的生物活性和潜在的治疗用途。从相应的叔丁基二甲基硅基保护肌苷出发，我们开发出了一种高效制备高官能度 N6 取代腺苷的方法。该方法的关键步骤是在 PyBroP 的存在下，在适当取代的肌苷和胺之间进行微波辅助胺化反应。使用受阻胺可以获得高产率的所需 N6 取代腺苷，而且该反应还能适应肌苷前体上的一系列取代基。
• Nolsoe, Jens M. J.; Gundersen, Lise-Lotte; Rise, Frode, Synthetic Communications, 1998, vol. 28, # 23, p. 4303 - 4315
  作者：Nolsoe, Jens M. J.、Gundersen, Lise-Lotte、Rise, Frode

  DOI：——

  日期：——
• 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.