1-(5-溴戊基)-5-甲基嘧啶-2,4-二酮 | 31167-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1-(5-溴戊基)-5-甲基嘧啶-2,4-二酮
• 英文名称: 1-(5-bromopentyl)thymine
• 英文别名: 1-(5-Brom-pentyl)-thymin；1-(5-Bromopentyl)-5-methylpyrimidine-2,4-dione
• CAS: 31167-27-8
• 化学式: C₁₀H₁₅BrN₂O₂
• 分子量: 275.145
• InChiKey: HUGAFVUVDHVVDE-UHFFFAOYSA-N

物化性质

• 密度：
  1.388±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-甲基腺素 、 1-(5-溴戊基)-5-甲基嘧啶-2,4-二酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以22%的产率得到N⁶-methyl-9-[5-(thymin-1-yl)pentyl]adenine
  参考文献：
  名称：

  Stacking Conformation of 9-[ω-(Thymin-1-yl)alkyl]adenine in Aqueous Solution

  摘要：

  An intramolecular stacking between adenine and thymine rings of 9-[w-(thymin-1-yl)alkyl]adenine was investigated by means of NMR and UV spectroscopy. The stacking conformation was presumed on the basis of the temperature dependence on the chemical shifts of the adenine and thymine ring protons in the buffer solution at pD 7.0.

  DOI：

  10.1081/ncn-120021430
• 作为产物：
  描述：

  胸腺嘧啶 生成 1-(5-溴戊基)-5-甲基嘧啶-2,4-二酮
  参考文献：
  名称：

  与dna插入分子有关的合成模型，研究了8-烷氧基补骨脂素和胸腺嘧啶之间的环-环堆积相互作用。

  摘要：

  作为补骨脂蛋白与DNA的插入和光结合的问题的一个贡献，制备了其中补骨脂素环通过聚亚甲基桥与胸腺嘧啶连接的模型化合物。通过UV中的变色测量来评估模型中的环-环分子内相互作用。

  DOI：

  10.1016/s0040-4039(01)90286-2

文献信息

• NMR and UV Study of 1,1′-(<i>α</i>,<i>ω</i>-Alkanediyl)bis[thymine] and 1,1′-(<i>α</i>,<i>ω</i>-Alkanediyl)bis[uracil]
  作者：Toshio Itahara

  DOI：10.1246/bcsj.70.2239

  日期：1997.9

  Treatment of thymine or uracil with Br(CH2)nBr (n = 3—10) in the presence of t-BuOK gave 1,1′-(α,ω-alkanediyl)bis[thymine] or 1,1′-(α,ω-alkanediyl)bis[uracil] together with 1-(ω-bromoalkyl)thymine or 1-(ω-bromoalkyl)uracil. The structures of these products were determined on the basis of the coupling constants between 5- and 3-positions of uracil ring on the 1H NMR spectra. Molecular aggregation of the thymine and uracil rings of these compounds in aqueous solution was studied on the basis of their 1H NMR and UV spectra. A stacking interaction of the two thymine rings linked by shorter polymethylene chains such as trimethylene and tetramenthylene groups was observed.

  将胸腺嘧啶或尿嘧啶与Br(CH2)nBr（n = 3—10）在t-BuOK存在下处理，得到了1,1′-(α,ω-烷烃二基)双[胸腺嘧啶]或1,1′-(α,ω-烷烃二基)双[尿嘧啶]，以及1-(ω-溴烷基)胸腺嘧啶或1-(ω-溴烷基)尿嘧啶。这些产物的结构是基于尿嘧啶环中5位和3位之间的耦合常数在1H NMR光谱上的分析来确定的。基于它们的1H NMR和紫外光谱，研究了这些化合物在水溶液中胸腺嘧啶和尿嘧啶环的分子聚集情况。观察到由较短的聚亚 methylene 链（如三亚甲基和四亚甲基基团）连接的两个胸腺嘧啶环之间存在堆叠相互作用。
• Customizable and Regioselective One‐Pot N−H Functionalization of DNA Nucleobases to Create a Library of Nucleobase Derivatives for Biomedical Applications
  作者：Djenisa H. A. Rocha、Carmen M. Machado、Vera Sousa、Cristiana F. V. Sousa、Vera L. M. Silva、Artur M. S. Silva、João Borges、João F. Mano

  DOI：10.1002/ejoc.202100786

  日期：2021.8.20

  synthetic procedures for producing a library of nucleobase derivatives enlisted with reactive functional groups for bioconjugation and cross-linking reactions with other biomolecules are reported. The nucleobase derivatives bearing either N-alkyl, N-propanenitrile, N-allyl or N-propargyl terminals are non-cytotoxic, denoting great promise for biomedical applications.

  一锅合成程序用于生产核碱基衍生物库，该库具有反应性官能团，用于与其他生物分子进行生物共轭和交联反应。带有N - 烷基、N - 丙腈、N - 烯丙基或N -炔丙基末端的核碱基衍生物是无细胞毒性的，在生物医学应用方面具有广阔的前景。
• Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity
  作者：Sofia Gabellone、Davide Piccinino、Silvia Filippi、Tiziana Castrignanò、Claudio Zippilli、Davide Del Buono、Raffaele Saladino

  DOI：10.3390/ijms23020915

  日期：——

  We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

  我们在此报告合成了一种新型嘧啶类生物模拟光附加物，其在核碱基之间带有烷基间隔，并对过表达人类拓扑异构酶1（TOP1）的两种突变癌细胞系SKMEL28和RPMI7951表现出抗黑色素瘤活性。其中，Dewar价态光附加物的选择性指数高于相应的嘧啶-（6-4）-嘧啶酮和环丁烷对应物，并通过分子对接分析评估了其与TOP1/DNA复合物之间的最高亲和力。新型光附加物的抗黑色素瘤活性在载入UV光保护木质素纳米粒子作为稳定剂和高效药物输送系统后得以保留。总体而言，这些结果支持一种结合抗黑色素瘤和UV防晒策略，涉及使用光保护木质素纳米粒子对皮肤上的胸腺嘧啶二聚体进行控制释放，随后将其牺牲性转化为光附加物，并连续抑制黑色素瘤和警觉细胞UV机制修复途径。
• Ground and excited-state interactions of coumarin and nucleotide base
  作者：Grażyna Wenska、Stefan Paszyc

  DOI：10.1139/v88-087

  日期：1988.3.1

  Steady-state and time-resolved fluorescence measurements for a series of bichromophoric compounds containing 7-methoxy-coumarin and nucleotide base residues have been performed in water and in organic solvents. The data from these studies have been used to calculate the relative proportion of folded and extended conformations of bichromophores. Ground-state stacking interactions of coumarin and nucleotide base have been found to be limited to aqueous solution. The contribution of the dynamic quenching mechanism to the total fluorescence quenching in water has been estimated. The absence of dynamic quenching in organic solvents is.explained on the basis of the very short lifetime of the fluorophore in methanol.

  在水和有机溶剂中，对一系列含有7-甲氧基香豆素和核苷酸碱基残基的二色性化合物进行了稳态和时间分辨荧光测量。这些研究的数据被用来计算二色荧光团的折叠和展开构象的相对比例。在水溶液中，发现香豆素和核苷酸碱基的基态堆叠相互作用受到限制。估计了动态猝灭机制对水中总荧光猝灭的贡献。在有机溶剂中缺乏动态猝灭机制是基于甲醇中荧光团寿命非常短的原因解释的。
• Synthesis of acyclic and macrocyclic analogs of Di-, Tri-, and tetranucleotides
  作者：V. E. Semenov、V. D. Akamsin、V. S. Reznik

  DOI：10.1134/s1070363207080233

  日期：2007.8

  Compounds consisting of two or three uracil fragments were synthesized by reaction of methyl-substituted uracil sodium salts with 1-(6-bromohexyl)-3,6-dimethyluracil or 1,6-dibromohexane. Treatment of these compounds with paraformaldehyde gave the corresponding pyrimidinophanes and acyclic compounds in which the uracil fragments are linked through methylene bridges. Uracil derivatives having no substituent on N-3 were synthesized by reactions of silylated uracils with 1,3-bis(6-bromohexyl)uracil or 4,4'-(6-bromohexyloxy)diphenylmethane. The acyclic compound was converted into pyrimidinophane containing uracil fragments with (NH)-H-3 groups. A trinucleotide analog including uracil and two adenine fragments was synthesized from 1,3-bis(6-bromohexyl)uracil.