8-bromo-N¹-[(2-acetoxyethoxy)-methyl]-5'-O-(tert-butyldimethylsilyl)-2',3'-O-isopropylideneinosine | 444989-14-4

• 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-bromo-N¹-[(2-acetoxyethoxy)-methyl]-5'-O-(tert-butyldimethylsilyl)-2',3'-O-isopropylideneinosine
• 英文别名: 2-[[9-[(3aR,4R,6R,6aR)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-6-oxopurin-1-yl]methoxy]ethyl acetate
• CAS: 444989-14-4
• 化学式: C₂₄H₃₇BrN₄O₈Si
• 分子量: 617.569
• InChiKey: FVHPPNMFJCZLGT-QTQZEZTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.33
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  8-bromo-N¹-[(2-acetoxyethoxy)-methyl]-5'-O-(tert-butyldimethylsilyl)-2',3'-O-isopropylideneinosine 在 吡啶 、 四氮唑 、 甲醇 、 四丁基氟化铵 、 sodium methylate 作用下， 以 四氢呋喃 为溶剂， 反应 54.0h， 生成 9-[(3aR,4R,6R,6aR)-6-(dianilinophosphoryloxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-1-(2-hydroxyethoxymethyl)purin-6-one
  参考文献：
  名称：

  Syntheses and Calcium-Mobilizing Evaluations of N-Glycosyl-Substituted Stable Mimics of Cyclic ADP-Ribose

  摘要：

  Cyclic ADP-ribose (cADPR) is not only a potent endogenous calcium modulator but also a second messenger. However, studies on the mechanism of cADPR action were limited due to its instability and lack of available structural modifications in the N-1-glyosyl unit of cADPR. In the present work, a series of N-1-glycosyl mimics with different configurational glycosyls or an ether strand were designed and synthesized mimicking the furanose ring. S(N)2 substitutions were carried out between the protected inosine and glycosyl triflates to form the N-1-glycosylinosine derivatives, accompanied with some O-6-glyeosyl-substituted as side products. The intramolecular cyclization was followed the strategy described by Matsuda et al. It was found that the 8-unsubstituted substrate could also be used to construct the intramolecular cyclic pyrophosphate. The activities of NI-glycosyl-substituted cADPR mimics were evaluated by induced Ca2+ release in rat brain microsomes and HeLa cells. It was found that the configuration of the N-1-glycosyl moiety in cADPR is not a critical structural factor for retaining the activity of mobilizing Ca2+ release. More interestingly, the N-1-acyclic analogue 6 exhibited strong activity by inducing Ca2+ release in both rat brain microsomes and HeLa cells. It constitutes a useful tool for further studies.

  DOI：

  10.1021/jm010530l
• 作为产物：
  描述：

  2-(氯甲氧基)乙酸乙酯 、 5'-O-TBDMS-2',3'-O-isopropylidene-8-bromoinosine 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 生成 8-bromo-N¹-[(2-acetoxyethoxy)-methyl]-5'-O-(tert-butyldimethylsilyl)-2',3'-O-isopropylideneinosine
  参考文献：
  名称：

  Trifluoromethylated cyclic-ADP-ribose mimic: synthesis of 8-trifluoromethyl-N1-[(5′′-O-phosphorylethoxy)methyl]-5′-O-phosphorylinosine-5′,5′′-cyclic pyrophosphate (8-CF3-cIDPRE) and its calcium release activity in T cells

  摘要：

  首先应用了一种便捷的三氟甲基化方法合成8-三氟甲基嘌呤核苷。在此基础上,研发了新颖的保护和去保护策略,顺利合成了三氟甲基化环状ADP核糖模拟物,即8-CF\({}_{3}\)-cIDPRE 1。利用完整、装载了fura-2的Jurkat T细胞,化合物1和2′,3′-O-异亚丙基-8-CF\({}_{3}\)-cIDPRE 14被鉴定为膜渗透性cADPR激动剂。与主要作为细胞内cADPR拮抗剂的8-取代cADPR类似物相反,8-取代cIDPRE衍生物显示为钙动员激动剂。本文报道,即使化合物1,即含有强吸电子CF\({}_{3}\)基团的8-取代cIDPRE,在T细胞中亦表现激动剂性质。有趣的是,部分保护的2′,3′-O-异亚丙基-8-CF\({}_{3}\)-cIDPRE也激活了钙信号,表明cADPR南侧核糖上的羟基对其生物活性仅有微小作用。据我们所知,8-CF\({}_{3}\)-cIDPRE 1是首个报道的含氟cADPR模拟物,而8-CF\({}_{3}\)-cIDPRE 1及化合物14则是阐明cADPR作用机制的有前景的分子探针。

  DOI：

  10.1039/c0ob00090f

文献信息

• Chemical synthesis and calcium release activity of N 1 -ether strand substituted cADPR mimic
  作者：Li-Jun Huang、Yong-Yuan Zhao、Lan Yuan、Ji-Mei Min、Li-He Zhang

  DOI：10.1016/s0960-894x(02)00033-1

  日期：2002.3

  8-Chloro cyclic inosine 5'-diphosphate ethoxymethyl ether 3 was synthesized by means of chemical method from protected inosine via phenylthio-type biphosphate substrate. The detection of Ca2+ release activity shows that 3 is a potent agonist of cADPR and has activity in intact Hela cells. (C) 2002 Elsevier Science Ltd. All rights reserved.