8-溴-2',3'-O-(1-甲基乙亚基)-肌苷 | 23339-40-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 8-溴-2',3'-O-(1-甲基乙亚基)-肌苷
• 英文名称: 2',3'-O-isopropylidene-8-bromoinosine
• 英文别名: 8-bromo-2',3'-O-isopropylideneinosine；2',3'-isopropylidene-8-bromoinosine；9-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-8-bromo-3H-purin-6-one
• CAS: 23339-40-4
• 化学式: C₁₃H₁₅BrN₄O₅
• 分子量: 387.19
• InChiKey: KLOATYJAXKWYHS-IOSLPCCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-溴-2',3'-O-(1-甲基乙亚基)-肌苷 在 四氮唑 、 18-冠醚-6 、 triisopropylbenzenesulfonyl chloride 、 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 吡啶 、 乙二醇二甲醚 为溶剂， 生成 8-bromo-N-1-[(1R,2S,3R,4R)-2,3-(isopropylidenedioxy)-4-[[(bisphenylthiophosphoryl)oxy]methyl]cyclopentyl]-5'-O-(dianilinophosphoryl)-2',3'-O-isopropylideneinosine
  参考文献：
  名称：

  Synthetic studies of carbocyclic analogs of cyclic ADP-ribose. Formation of a cyclic dimer, a 36-membered-ring product, in the condensation reaction of an 8-bromo-N1-[5-(phenylthiophosphoryl)carbocyclic-ribosyl]inosine 5′-phosphate derivative mediated by AgNO3

  摘要：

  Formation of symmetric 36-membered-ring product 14 was observed in the synthetic study of a stable mimic of cyclic ADP-ribose (cADPR, 1), When 8-bromo-N-1-[5-(phenylthiophosphoryl)carbocyclic-ribosyl]inosine 5'-phosphate derivative 5 was treated with AgNO3 and Et3N in N-methyl-2-pyrrolidinone-HMPA (3:1), the substrate was dimerized and cyclized to give 14 in 39% yield, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01575-5
• 作为产物：
  描述：

  8-bromo-2',3'-O-isopropylene adenosine 在 sodium nitrite 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 16.0h， 以83%的产率得到8-溴-2',3'-O-(1-甲基乙亚基)-肌苷
  参考文献：
  名称：

  环状腺苷 5'-二磷酸核糖受体激动剂的全合成

  摘要：

  稳定的环状腺苷 5'-二磷酸核糖 (cADPR) 类似物是化学生物学工具，可以探测这种新兴的强效第二信使的 Ca 2+释放机制和构效关系。然而，由于难以产生敏感的N 1-核糖基连接，因此无法获得具有完整“北”核糖的类似物。我们报告了膜渗透性、水解稳定的 cADPR 受体激动剂 8-Br- N 1-cIDPR 通过受保护的 8-溴肌苷的区域选择性和立体选择性N 1-核糖基化的首次全合成。

  DOI：

  10.1021/jo202319f

文献信息

• 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
  作者：Min Dong、Tanja Kirchberger、Xiangchen Huang、Zhen Jun Yang、Liang Ren Zhang、Andreas H. Guse、Li He Zhang

  DOI：10.1039/c0ob00090f

  日期：——

  A convenient trifluoromethylation method was firstly applied to the synthesis of 8- CF3-purine nucleosides. On the basis of this method, new protection and deprotection strategies were developed for the successful synthesis of the trifluoromethylated cyclic-ADP-ribose mimic, 8-CF3-cIDPRE 1. Using intact, fura-2-loaded Jurkat T cells compound 1 and 2′,3′-O-isopropylidene 8-CF3-cIDPRE 14 were characterized as membrane-permeant cADPR agonists. Contrary to the 8-substituted cADPR analogues that mainly act as antagonists of cADPR in cells, 8-substituted cIDPRE derivatives were shown to be Ca2+ mobilizing agonists. Here we report that even compound 1, the 8-substituted cIDPRE with the strong electron withdrawing CF3 group, behaves as an agonist in T cells. Interestingly, also the partially protected 2′,3′-O-isopropylidene 8-CF3-cIDPRE activated Ca2+ signaling indicating only a minor role for the hydroxyl groups of the southern ribose of cADPR for its biological activity. To our knowledge 8-CF3-cIDPRE 1 is the first reported fluoro substituted cADPR mimic and 8-CF3-cIDPRE 1 and compound 14 are promising molecular probes for elucidating the mode of action of cADPR.

  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。
• Concise synthesis of novel acyclic analogues of cADPR with an ether chain as the northern moiety
  作者：Huimin Wu、Zhenjun Yang、Liangren Zhang、Lihe Zhang

  DOI：10.1039/b9nj00595a

  日期：——

  To study the properties of hydrolysates of cyclic adenosine diphosphate ribose (cADPR), a series of novel acyclic analogues of cADPR with an ether chain as the northern moiety and 8-substituted adenine or hypoxanthine as the base moiety were synthesized via an N1 substitution construction, followed by bisphosphorylation, phosphoramidition or pyrophosphorylation. These compounds also provide various precursors for synthesizing cADPR analogues.

  为了研究环腺苷二磷酸核糖（cADPR）水解产物的性质，合成了一系列以醚链作为北基团，8取代腺嘌呤或次黄嘌呤作为碱基团的新型无环类cADPR类似物，合成过程包括N1取代反应，随后进行双磷酸化、磷酰胺化或焦磷酸化。这些化合物还提供了合成cADPR类似物的多种前体。
• Nucleosides and Nucleotides. 173. Synthesis of Cyclic IDP-carbocyclic-ribose, a Stable Mimic of Cyclic ADP-ribose. Significant Facilitation of the Intramolecular Condensation Reaction of <i>N</i>-1-(Carbocyclic-ribosyl)inosine 5‘,6‘‘-Diphosphate Derivatives by an 8-Bromo-Substitution at the Hypoxanthine Moiety
  作者：Satoshi Shuto、Michiyo Shirato、Yuji Sumita、Yoshihito Ueno、Akira Matsuda

  DOI：10.1021/jo9717797

  日期：1998.3.1

  Cyclic ADP-ribose (cADPR, 1) is a general mediator involved in cellular Ca2+ signaling. However, both the biological and chemical instability of cADPR limit studies on its physiological role. We designed cyclic ADP-carbocyclic-ribose (3) and its inosine congener 4 as stable mimics of cADPR and successfully synthesized 4. Starting with cyclopentadiene, the optically active carbocyclic unit 8 was constructed via enzymatic optical resolution. S(N)2 reactions of 8 with inosine derivative 7 and the 8-bromoinosine derivative 25 gave the N-1-substituted derivatives 6 and 26, which were converted to the corresponding diphosphate derivatives 5 and 22. The intramolecular condensation reactions between the two phosphate groups of 5 and 22 were investigated, Although the reaction with inosine derivative 5 did not produce any of the cyclization product 20, treatment of the corresponding 8-bromoinosine derivative 22 with EDC gave the desired intramolecular condensation product 29 in 23% yield. Thus, the significant effect of the 8-bromo group at the hypoxanthine moiety in facilitating the key intramolecular condensation reaction between the phosphate groups of the substrate 22 was recognized. This is possibly due to conformational restriction of the molecule in a syn-form around its glycosyl linkage. The 8-bromo and isopropylidene groups were removed in succession to give the target compound 4. This is the first total synthesis of this type of cyclic nucleotide.
• Minamoto, Katsumaro; Fujiki, Yasumi; Shiomi, Niro, Journal of the Chemical Society. Perkin transactions I, 1985, p. 2337 - 2346
  作者：Minamoto, Katsumaro、Fujiki, Yasumi、Shiomi, Niro、Uda, Yoriaki、Sasaki, Tadashi

  DOI：——

  日期：——
• Synthetic studies of carbocyclic analogs of cyclic ADP-ribose. Formation of a cyclic dimer, a 36-membered-ring product, in the condensation reaction of an 8-bromo-N1-[5-(phenylthiophosphoryl)carbocyclic-ribosyl]inosine 5′-phosphate derivative mediated by AgNO3
  作者：Satoshi Shuto、Michiyo Shirato、Yuji Sumita、Yoshihito Ueno、Akira Matsuda

  DOI：10.1016/s0040-4039(98)01575-5

  日期：1998.10

  Formation of symmetric 36-membered-ring product 14 was observed in the synthetic study of a stable mimic of cyclic ADP-ribose (cADPR, 1), When 8-bromo-N-1-[5-(phenylthiophosphoryl)carbocyclic-ribosyl]inosine 5'-phosphate derivative 5 was treated with AgNO3 and Et3N in N-methyl-2-pyrrolidinone-HMPA (3:1), the substrate was dimerized and cyclized to give 14 in 39% yield, (C) 1998 Elsevier Science Ltd. All rights reserved.