O-6-benzylinosine | 42204-35-3

• 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: O-6-benzylinosine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-5-(6-phenylmethoxypurin-9-yl)oxolane-3,4-diol
• CAS: 42204-35-3
• 化学式: C₁₇H₁₈N₄O₅
• 分子量: 358.354
• InChiKey: YKCFRYNFIUFWOG-LSCFUAHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  O-6-benzylinosine 在 disodium hydrogen arsenate heptahydrate 、 recombinant E_. coli purine nucleoside phosphorylase 作用下， 以 aq. buffer 为溶剂， 反应 16.0h， 以85%的产率得到6-苄氧基嘌呤
  参考文献：
  名称：

  从核苷化学酶促合成细胞分裂素：核糖作为封闭基团†

  摘要：

  核苷磷酸化酶参与核苷生物合成的挽救途径，并催化核碱基与α - D-核糖-1-磷酸的可逆反应，生成相应的核苷和无机磷酸盐。这些反应的平衡向核苷转移，特别是在嘌呤的情况下。嘌呤核苷磷酸化酶（PNP，EC 2.4.2.1）在实验室和工业中广泛用于合成具有实际重要性的核苷。细菌PNP利用相对广泛的具有不同取代基的嘌呤形成相应的核苷，具有相对较宽的底物特异性。为了使反应朝相反的方向进行，我们使用了砷解作用而不是磷解作用。由于生成的α-的水解，该反应是不可逆的D-核糖-1-砷。结果，杂环碱以定量产率形成并且可以容易地分离。我们已经开发出一种新的细胞分裂素制备方法，该方法基于在PNP和Na 2 HAsO 4存在下酶解N 6取代的腺苷的N-糖苷键的方法。根据HPLC分析，转化以定量产率进行。在提出的策略中，核糖残基充当保护基。最终产品具有的ASO无污染4 3-已经检测到通过HPLC-HRMS; 已经提出了通过ESI-MS进行简单的砷分析检测。

  DOI：

  10.1039/c8ob00223a
• 作为产物：
  描述：

  2’,3’,5’-三乙酰肌苷 在 4-二甲氨基吡啶 、 氨 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 22.34h， 生成 O-6-benzylinosine
  参考文献：
  名称：

  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

  摘要：

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

  DOI：

  10.1021/acs.jmedchem.5b00802

文献信息

• N6-isopentenyladenosine a new potential anti-angiogenic compound that targets human microvascular endothelial cells <i>in vitro</i>
  作者：Sara Castiglioni、Valentina Romeo、Silvana Casati、Roberta Ottria、Cristiana Perrotta、Pierangela Ciuffreda、Jeanette A. M. Maier

  DOI：10.1080/15257770.2018.1503673

  日期：2018.10.3

  significant reduction of cell viability, upregulated p21 and promoted caspase-3 cleavage in a dose dependent manner leading to apoptotic cell death as detected by FACS analysis. To understand structure-function relationship of N6-isopentenyladenosine, we investigated the effect of some N6-isopentenyladenosine analogs. Our results suggest that N6-isopentenyladenosine and some of its derivatives are potentially

  摘要 N6-异戊烯基腺苷是一种对正常细胞和肿瘤细胞具有抗增殖和促凋亡作用的非典型核苷。考虑到血管生成在各种疾病中的作用，我们研究了 N6-异戊烯基腺苷对人微血管内皮细胞（血管生成的主角）的细胞毒作用。我们的结果表明，N6-异戊烯基腺苷以剂量依赖性方式诱导细胞活力的显着降低，上调 p21 并促进 caspase-3 切割，导致 FACS 分析检测到的细胞凋亡。为了了解 N6-异戊烯基腺苷的结构-功能关系，我们研究了一些 N6-异戊烯基腺苷类似物的作用。
• N6-substituted adenosines. Cytokinin and antitumor activities
  作者：Svetlana V. Kolyachkina、Vitali I. Tararov、Cyril S. Alexeev、Dmitry M. Krivosheev、Georgy A. Romanov、Evgenia V. Stepanova、Eliso S. Solomko、Andrey N. Inshakov、Sergey N. Mikhailov

  DOI：10.1135/cccc2011114

  日期：——

  A series of N⁶-adenosine derivatives were synthesized by alkylation of N⁶-acetyl-2′,3′,5′-tri-O-acetyladenosine (1) with alkyl halides and alcohols. It was shown that propargyl derivative 2a is a good substrate for copper(I) catalyzed Huisgen [3+2] cycloaddition with azides. This click-reaction can be used for preparation of the libraries of 1,2,3-triazolyl modified adenosines. Biological activities of N⁶-adenosines were studied in two plant and six human cancer cell assays. The remarkable parallel between cytokinin and cytotoxic activities was found. The most cytokinin active compounds 3c–3e at the same time appeared to be the most potent cytotoxic agents.

  一系列的N6-腺苷衍生物通过烷基卤化物和醇对N6-乙酰-2'，3'，5'-三-O-乙酰基腺苷（1）进行烷基化合成。结果表明，丙炔基衍生物2a是铜（I）催化的Huisgen [3+2]环加成与叠氮化物反应的良好底物。此点击反应可用于制备1,2,3-三唑基修饰的腺苷库。在两种植物和六种人类癌细胞测试中研究了N6-腺苷的生物活性。发现细胞分裂素和细胞毒性活性之间存在显著的平行关系。同时，最具细胞分裂素活性的化合物3c-3e也被证明是最有效的细胞毒性剂。
• High-Throughput Five Minute Microwave Accelerated Glycosylation Approach to the Synthesis of Nucleoside Libraries
  作者：Brett C. Bookser、Nicholas B. Raffaele

  DOI：10.1021/jo061885l

  日期：2007.1.1

  [GRAPHICS]The Vorbruggen glycosylation reaction was adapted into a one-step 5 min/130 degrees C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl triflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield +/- SD was 26 +/- 16%, and the average purity +/- SD was 95 +/- 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
• Synthesis of 2′-Substituted Inosine Analogs via Unusual Masking of the 6-Hydroxyl Group
  作者：Fabio Casu、Rebecca K. Harston、Maria A. Chiacchio、Giuseppe Gumina

  DOI：10.1080/15257770.2011.650254

  日期：2012.3

  2'-Modified inosine analogs have been synthesized from 6-chloropurine riboside via 6-dimethylaminopurine or 6-benzyloxypurine intermediates. The dimethylaminopurine intermediate was obtained via an unusually facile dimethylamine transfer from dimethylformamide.
• ADENOSINE COMPOUND AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：Nikken Chemicals Company, Limited

  公开号：EP1303528A1

  公开（公告）日：2003-04-23