1-(2-deoxy-β-D-erythro-pentofuranosyl)-3-(octa-1,7-diynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 1-(2-deoxy-β-D-erythro-pentofuranosyl)-3-(octa-1,7-diynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: 7-octadiyne-8-aza-7-deaza-2'-deoxyadenosine；1-[2-deoxy-β-D-erythropentofuranosyl]-3-(octa-1,7-diyn-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine；8-aza-7-deaza-7-(octa-1,7-diyn-1-yl)-2'-deoxyadenosine；(2R,3S,5R)-5-(4-amino-3-octa-1,7-diynylpyrazolo[3,4-d]pyrimidin-1-yl)-2-(hydroxymethyl)oxolan-3-ol
• 化学式: C₁₈H₂₁N₅O₃
• 分子量: 355.396
• InChiKey: TUPJYVHMDOAACN-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-β-D-erythro-pentofuranosyl)-3-(octa-1,7-diynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 吡啶 作用下， 以 甲醇 为溶剂， 反应 6.5h， 生成 1-[2-deoxy-5-O-(4,4'-dimethoxytrityl)-β-D-erythropentofuranosyl]-4-{[(N,N-dimethylamino)methylidene]amino}-3-(octa-1,7-diyn-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  8-Aza-7-deazaadenine-DNA的叠氮化物-炔基“点击”偶联：合成，双链稳定性和荧光染料标记

  摘要：

  描述了通过Huisgen-Meldal-Sharpless“点击”反应对DNA进行的内部染料标记。荧光9-叠氮基甲基蒽2和3-叠氮基-7-羟基香豆素3被用于寡核苷酸的后合成功能化结合八-（1,7）-二炔基-8-氮杂-7-脱氮基2'-脱氧腺苷1。通过Sonogashira交叉偶联从相应的7-碘化合物制备核苷1，将其转化为相应的亚磷酰胺，并合成寡核苷酸。要评估配体对寡核苷酸双链体稳定性的影响，请使用叠氮化苄4（非极性）和2'，3'-二脱氧叠氮胸苷5（AZT）（极性）与荧光染料2和3一起引入。具有八-1,7-二炔基侧链（即含有1）的DNA双链体比含有8-aza-7-deaza-2'-脱氧腺苷的寡核苷酸更稳定，这表明该侧链具有空间自由度。蒽残基的单个缀合导致双链体熔化的T m增加9°C 。与7-deazaadenine染料缀合物相反，8-aza-7-deazaadenine缀合物几乎没有荧光猝灭，

  DOI：

  10.1021/bc100090y
• 作为产物：
  描述：

  1,7-辛二炔 在 甲醇 、 copper(l) iodide 、 四(三苯基膦)钯 、 氨 、 sodium methylate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 1-(2-deoxy-β-D-erythro-pentofuranosyl)-3-(octa-1,7-diynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  8-Aza-7-deazaadenine-DNA的叠氮化物-炔基“点击”偶联：合成，双链稳定性和荧光染料标记

  摘要：

  描述了通过Huisgen-Meldal-Sharpless“点击”反应对DNA进行的内部染料标记。荧光9-叠氮基甲基蒽2和3-叠氮基-7-羟基香豆素3被用于寡核苷酸的后合成功能化结合八-（1,7）-二炔基-8-氮杂-7-脱氮基2'-脱氧腺苷1。通过Sonogashira交叉偶联从相应的7-碘化合物制备核苷1，将其转化为相应的亚磷酰胺，并合成寡核苷酸。要评估配体对寡核苷酸双链体稳定性的影响，请使用叠氮化苄4（非极性）和2'，3'-二脱氧叠氮胸苷5（AZT）（极性）与荧光染料2和3一起引入。具有八-1,7-二炔基侧链（即含有1）的DNA双链体比含有8-aza-7-deaza-2'-脱氧腺苷的寡核苷酸更稳定，这表明该侧链具有空间自由度。蒽残基的单个缀合导致双链体熔化的T m增加9°C 。与7-deazaadenine染料缀合物相反，8-aza-7-deazaadenine缀合物几乎没有荧光猝灭，

  DOI：

  10.1021/bc100090y

文献信息

• 7-Substituted 7-Deaza-2′-deoxyadenosines and 8-Aza-7-deaza-2′-deoxyadenosines: Fluorescence of DNA-Base Analogues Induced by the 7-Alkynyl Side Chain
  作者：Frank Seela、Matthias Zulauf、Markus Sauer、Michael Deimel

  DOI：10.1002/(sici)1522-2675(20000510)83:5<910::aid-hlca910>3.0.co;2-4

  日期：2000.5.10

  the 7-alkynylated 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin-4-amine) 2′-deoxyribonucleosides are rather weakly fluorescent (Table 4). Quantum yields and fluorescence decay times are measured. The synthesis of the 7-alkynylated 7-deaza-2′-deoxyadenosines and 8-aza-7-deaza-2′-deoxyadenosines was performed with 7-deaza-2′-deoxy-7-iodoadenosine (6) or 8-aza-7-deaza-2′-deoxy-7-iodoadenosine (22) as

  7-炔基化的 7-deazaadenine（吡咯并[2,3-d]嘧啶-4-胺）2'-脱氧核糖核苷显示出由 7-炔基侧链诱导的强荧光（表 3）。当该化合物在 280 nm 处照射时，观察到发射约 400 nm 的大斯托克斯位移。溶剂依赖性表明带电过渡态的形成。当三键与杂环碱基共轭时出现荧光。三键上的给电子取代基会增加荧光，而吸电子残基会降低荧光。相比之下，7-炔基化的 8-aza-7-deazaadenine（吡唑并[3,4-d]嘧啶-4-胺）2'-脱氧核糖核苷的荧光相当弱（表 4）。测量量子产率和荧光衰减时间。用 7-deaza-2'-deoxy-7-iodoadenosine (6) 或 8-aza 合成 7-炔基化的 7-deaza-2'-deoxyadenosines 和 8-aza-7-deaza-2'-deoxyadenosines -7-deaza-2'-deoxy-7-iodoadenosine
• High-Density Functionalization and Cross-Linking of DNA: “Click” and “Bis-Click” Cycloadditions Performed on Alkynylated Oligonucleotides with Fluorogenic Anthracene Azides
  作者：Suresh S. Pujari、Sachin A. Ingale、Frank Seela

  DOI：10.1021/bc5003532

  日期：2014.10.15

  density functionalization of DNA with ethynyl and octadiynyl side chains followed by CuAAC “click labeling” with 9-azidomethylanthracene was performed. Alkynyl DNA was also cross-linked with fluorogenic 9,10-bis-azidomethylanthracene employing the “bis-click” reaction. By this means the fluorescence of the anthracene moiety was imparted to the virtually nonfluorescent DNA. Phosphoramidites of 8-aza-

  用乙炔基和辛二炔基侧链对DNA进行高密度功能化，然后用9-叠氮基甲基蒽进行CuAAC“点击标记”。还使用“双点击”反应将炔基DNA与荧光9,10-双-叠氮基甲基蒽交联。通过这种方式，蒽部分的荧光被赋予了实际上非荧光的DNA。在固相寡聚脱氧核苷酸合成中使用具有短和长接头臂的8-氮杂-7-脱氮杂-2'-脱氧腺苷的亚磷酰胺。发现高密度的炔基化DNA（无蒽残基）在长连接臂和短连接臂上都具有相当的稳定性。与长连接子连接相比，短连接子的高密度蒽官能化DNA不稳定。由具有荧光9,10-双-叠氮基甲基蒽的炔基化寡核苷酸构建的链间交联同二聚体与互补链杂交形成双螺旋。当连接器位于末端时，它们比在中心位置更稳定。与长接头加合物相比，短接头蒽加合物不稳定。荧光蒽残基不仅对双链体稳定性有显着影响，而且还赋予了该物种荧光性。当交联键处于末端位置时，具有长连接头连接性的交联双螺旋的荧光被淬灭，而当连接头在分子中心连接两个双螺旋时，该荧光被猝灭。
• Hydrogelation and spontaneous fiber formation of 8-aza-7-deazaadenine nucleoside ‘click’ conjugates
  作者：Frank Seela、Suresh S. Pujari、Andreas H. Schäfer

  DOI：10.1016/j.tet.2011.07.015

  日期：2011.9

  Nucleoside hydrogels based on benzyl azide 'click' conjugates of 8-aza-7-deaza-2'-deoxyadenosine bearing 7-ethynyl, 7-octa-(1,7-diynyl), and 7-tri-prop-2-ynyl-amine side chains were synthesized (1, 3, 4). The cycloaddition adduct with the shortest linker (1) yields the most powerful hydrogelator forming stable gels at a concentration of 0.3 wt % of 1 in water. One molecule of 1 catches 7500 water molecules. Cycloaddition of the 8-aza-7-deaza-7-azido-2'-deoxyadenosine (9) and 3-phenyl-1-propyne (10) leads to the isomeric conjugate 2, with a C-N connectivity between the nucleobase and triazole moiety. This gel is less stable than that of the adduct 1. Both gels show a similar stability over a wide pH range (4.0-10.0). Xerogels of 1 and 2 studied by scanning electron microscopy (SEM) reveal that both click adducts (1 and 2) form long fibers spontaneously. (C) 2011 Elsevier Ltd. All rights reserved.
• Cross-Linked DNA Generated by “Bis-click” Reactions with Bis-functional Azides: Site Independent Ligation of Oligonucleotides via Nucleobase Alkynyl Chains
  作者：Suresh S. Pujari、Hai Xiong、Frank Seela

  DOI：10.1021/jo101809w

  日期：2010.12.17

  Template-free cross-linking of single-stranded DNA bearing octadiynyl side chains at the 7-position of 8-aza-7-deazapurine moieties with bisfunctional azides is reported employing a Cu(I)-catalyzed azide alkyne "bis-click" reaction. Bis-adducts were formed when the bis-azide:oligonucleotide ratio was 1:1; monofunctionalization occurred when the ratio was 15:1. Four-stranded DNA consisting of two cross-linked duplexes was obtained after hydridization. Cross-linked duplexes are as stable as individual duplexes when ligation was introduced at terminal positions; ligation at a central position led to a slight duplex destabilization.
• 7-Deazapurine and 8-Aza-7-deazapurine Nucleoside and Oligonucleotide Pyrene “Click” Conjugates: Synthesis, Nucleobase Controlled Fluorescence Quenching, and Duplex Stability
  作者：Sachin A. Ingale、Suresh S. Pujari、Venkata Ramana Sirivolu、Ping Ding、Hai Xiong、Hui Mei、Frank Seela

  DOI：10.1021/jo202103q

  日期：2012.1.6

  7-Deazapurine and 8-aza-7-deazapurine nucleosides related to dA and dG bearing 7-octadiynyl or 7-tripropargylamine side chains as well as corresponding oligonucleotides were synthesized. "Click" conjugation with 1-azidomethyl pyrene (10) resulted in fluorescent derivatives. Octadiynyl conjugates show only monomer fluorescence, while the proximal alignment of pyrene residues in the tripropargylamine derivatives causes excimer emission. 8-Aza-7-deazapurine pyrene 'click" conjugates exhibit fluorescence emission much higher than that of 7-deazapurine derivatives. They are quenched by intramolecular charge transfer between the nucleobase and the dye. Oligonucleotide single strands decorated with two "double clicked" pyrenes show weak or no excimer fluorescence. However, when duplexes carry proximal pyrenes in complementary strands, strong excimer fluorescence is observed. A single replacement of a canonical nucleoside by a pyrene conjugate stabilizes the duplex substantially, most likely by stacking interactions: 6-12 degrees C for duplexes with a modified "adenine" base and 2-6 degrees C for a modified "guanine" base. The favorable photophysical properties of 8-aza-7-deazapurine pyrene conjugates improve the utility of pyrene fluorescence reporters in oligonucleotide sensing as these nucleoside conjugates are not affected by nucleobase induced quenching.