2',3',5'-tri-O-acetyl-8-bromoinosine | 55627-72-0

• 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: 2',3',5'-tri-O-acetyl-8-bromoinosine
• 英文别名: [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(8-bromo-6-oxo-1H-purin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 55627-72-0
• 化学式: C₁₆H₁₇BrN₄O₈
• 分子量: 473.237
• InChiKey: WQJUNBRUUJNMMY-SDBHATRESA-N

物化性质

• 密度：
  1.85±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2',3',5'-tri-O-acetyl-8-bromoinosine 在 氨 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以95%的产率得到8-溴肌苷
  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’-三乙酰肌苷 在 disodium hydrogenphosphate 、 溴 作用下， 以 1,4-二氧六环 为溶剂， 反应 168.0h， 以86%的产率得到2',3',5'-tri-O-acetyl-8-bromoinosine
  参考文献：
  名称：

  N6，C8分布的腺苷衍生物作为腺苷A1受体的部分激动剂。

  摘要：

  描述了腺苷的N6，C8-二取代衍生物作为腺苷受体潜在的部分激动剂的合成和生物学评估。通过三种途径，制备了两个系列的化合物，即N6-环戊基腺苷衍生物3a-e和C8-（环戊基氨基）腺苷类似物3e和9a-d。对其中一种化合物N6-乙基-8（环戊基氨基）腺苷（9b）进行了X射线结构测定（正交晶系，空间群P2（1）2（1）2（1）（第19号））其中a = 11.039（3），b = 8.708（2）和c = 24.815（12）埃，Z = 4，R1 = 0.0974，R2（W）= 0.2455）。由于分子内氢键，该化合物的核糖部分处于反构象。在放射配体结合研究中对化合物进行了体外测试，得出了它们对A1和A2a腺苷受体的亲和力。所有化合物都表现出对A1的选择性，亲和力在高纳摩尔，低微摩尔范围内。在A1受体上，还确定了所谓的GTP位移，即在存在和不存在1 mM GTP的情况下测得的亲和力之间的比率。所有GTP转换（介于1

  DOI：

  10.1021/jm950267m

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。
• Studies on organic fluorine compounds. Part 35. Trifluoromethylation of pyrimidine- and purine-nucleosides with trifluoromethyl–copper complex
  作者：Yoshiro Kobayashi、Kenjiro Yamamoto、Toyohira Asai、Masanori Nakano、Itsumaro Kumadaki

  DOI：10.1039/p19800002755

  日期：——

  Halogenated nucleoside derivatives were trifluoromethylated using a solution of a trifluoromethyl–copper complex, which was prepared by shaking trifluoromethyl iodide and copper powder in hexamethylphosphoric triamide and filtering off the excess of copper powder. The following trifluoromethylated nucleosides were obtained in moderate to good yields: 5-trifluoromethyl-uridine, -deoxyuridine, -cytidine

  使用三氟甲基-铜络合物的溶液将卤代的核苷衍生物进行三氟甲基化，该溶液是通过将三氟甲基碘和铜粉在六甲基磷酸三酰胺中振摇并滤出过量的铜粉而制得的。以中等至良好的产率获得以下三氟甲基化的核苷：5-三氟甲基-尿苷，-脱氧尿苷，-胞苷，-脱氧胞苷和-阿拉伯糖基胞嘧啶；8-三氟甲基-腺苷，-脱氧腺苷和-肌苷；和6-三氟甲基核呋喃呋喃糖基嘌呤。该程序提供了许多三氟甲基化合物的简单合成方法。
• Inhibition of Nucleoside Transport Proteins by <i>C</i>⁸-Alkylamine-Substituted Purines
  作者：Reynier A. Tromp、Ronald F. Spanjersberg、Jacobien K. von Frijtag Drabbe Künzel、Adriaan P. IJzerman

  DOI：10.1021/jm049303k

  日期：2005.1.1

  biological data of these compounds with 6-benzylthioinosine (4, K(i) = 53 nM) and 9-benzyl-6-(4-nitrobenzylsulfanyl)purine (59, K(i) = 135 nM) confirmed the hypothesis. The K(i) values improved upon elongation of the alkylamine chain from methylamine to n-hexylamine with an optimum for n-pentylamine (50, K(i) = 2.3 nM). Substitution with 2-methylbutylamine (52), cyclopropylamine (53), cyclopentylamine (54

  4-硝基苄基硫代肌苷（NBTI，1）是核苷转运蛋白ENT1的众所周知的抑制剂。在这里，我们报告了比NBTI极性小的化合物的合成和生物学评估。在我们实验室中的化合物筛选表明，在N（6）-环戊基腺苷（CPA，2）的C（8）位置引入烷基胺取代基会导致对转运蛋白的亲和力增加。研究了这是否也适用于NBTI衍生物。制备了两个系列的C（8）-烷基胺取代的化合物，一个不存在硝基（46-58），另一个不饱和核糖部分被苄基取代（72-75）。这些化合物与6-苄基硫代肌苷（4，K（i）= 53 nM）和9-苄基-6-（4-硝基苄基硫烷基）嘌呤（59，K（i）= 135 nM）证实了这一假设。当烷基胺链从甲胺延伸至正己胺时，K（i）值得到改善，正戊胺的最佳值（50，K（i）= 2.3 nM）。用2-甲基丁胺（52），环丙胺（53），环戊胺（54、72）和环己胺（55、73）取代显示存在大体积基团增强了亲和力。通过
• 6,8-DISUBSTITUTED PURINE COMPOSITIONS
  申请人：ZAHAJSKA Lenka

  公开号：US20130072506A1

  公开（公告）日：2013-03-21

  6,8-Disubstituted purines which can be used in drug and cosmetic compositions and/or applications are provided. These 6,8-disubstituted purines have a wide range of biological activities, including for example anti-inflammatory, anti-senescent, as well as well as other activities which are especially useful in pharmaceutical and cosmetic applications. The 6,8-disubstituted purine compounds and compositions containing such 6,8-disubstituted purines provide growth-regulatory, differentiating, antisenescent and antiaging properties with improved selectivities and efficiencies and lower toxicities than analogues known heretofore.

  提供可用于药物和化妆品组合物和/或应用的6,8-二取代嘌呤。这些6,8-二取代嘌呤具有广泛的生物活性，例如抗炎、抗衰老等，以及其他在制药和化妆品应用中特别有用的活性。含有这些6,8-二取代嘌呤的化合物和组合物提供生长调节、分化、抗衰老和抗衰老特性，具有比迄今为止已知的类似物更好的选择性和效率，以及较低的毒性。
• Production, Characterization and Synthetic Application of a Purine Nucleoside Phosphorylase from<i>Aeromonas hydrophila</i>
  作者：Daniela Ubiali、Carla D. Serra、Immacolata Serra、Carlo F. Morelli、Marco Terreni、Alessandra M. Albertini、Paolo Manitto、Giovanna Speranza

  DOI：10.1002/adsc.201100505

  日期：2012.1

  6‐aminopurine (deoxy)ribonucleosides. A library of nucleoside analogues was synthesized and then submitted to enzymatic phosphorolysis as well. This assay revealed that 1‐, 2‐, 6‐ and 7‐modified nucleosides are accepted as substrates, whereas 8‐substituted nucleosides are not. A few transglycosylation reactions were carried out using 7‐methylguanosine iodide (4) as a D‐ribose donor and 6‐substituted purines

  由deoD基因编码的嗜水气单胞菌的嘌呤核苷磷酸化酶（PNP）已在大肠杆菌中过表达，纯化，表征了其底物特异性，并用于一些6取代的嘌呤9-核糖苷的制备性合成。对天然核苷的底物特异性表明，该PNP催化6-氧代嘌呤和6-氨基嘌呤（脱氧）核糖核苷的磷酸水解。合成了核苷类似物的文库，然后也进行了酶促磷酸解。该测定法揭示了1、2、6和7修饰的核苷被接受为底物，而8取代的核苷则不被接受。使用7-甲基鸟苷碘化物进行了一些转糖基化反应（4）作为D核糖供体，6取代的嘌呤作为受体。特别是，按照这种方法，可以使用2-氨基-6氯嘌呤9核苷（2c），6-甲氧基嘌呤9核苷（2d）和2-氨基6（甲硫基）嘌呤9核苷（2g）合成的收率和纯度都很高。