1-(1-Pentynyl)-N⁴-acetylcytosine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(1-Pentynyl)-N⁴-acetylcytosine
• 英文别名: 4-acetyl-1-(pentyn-5-yl)cytosine；N-(2-oxo-1-pent-4-ynylpyrimidin-4-yl)acetamide
• 化学式: C₁₁H₁₃N₃O₂
• 分子量: 219.243
• InChiKey: DQOOHFUFGCHFSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(1-Pentynyl)-N⁴-acetylcytosine 在 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 27.0h， 以100%的产率得到4-amino-1-(pent-4-yn-1-yl)pyrimidin-2-one
  参考文献：
  名称：

  单击化学方法，将截短侧耳素与核苷或无环核苷衍生物偶联，并将其与细菌核糖体结合。

  摘要：

  截短侧耳素及其衍生物是通过与核糖体结合而抑制细菌中蛋白质合成的抗菌药物。为了促进基于截短侧耳素的药物的合理设计，通过点击化学方案合成了19种截短侧耳素作为侧链延伸的截短侧耳素缀合物。通过23S rRNA中核苷酸U2506的化学足迹评估结合，所有结合物均以不同程度结合，反映了其与肽基转移酶中心的结合亲和力。侧链延伸部分还在位置U2585处显示了各种保护。对具有最高亲和力的结合物的对接研究支持以下结论：尽管存在各种结合，截短侧耳素骨架仍在相同的结合袋中结合。共轭三唑部分的位置很好，核碱基位于50S核糖体亚基的不同口袋中。与截短侧耳素本身相比，具有最高亲和力和明显更好结合的衍生物包含与截短侧耳素C-22的腺嘌呤9-基丙烯三唑缀合物。

  DOI：

  10.1021/jm800261u
• 作为产物：
  描述：

  N4-乙酰胞嘧啶 、 5-碘-1-戊炔 在 potassium carbonate 、 二甲基亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以88%的产率得到1-(1-Pentynyl)-N⁴-acetylcytosine
  参考文献：
  名称：

  Cobalt-Mediated [2+2+2] Cycloadditions of Pyrimidine Derivatives to Alkynes

  摘要：

  The scope and limitations of the cobalt-mediated [2+2+2] cycloaddition of pyrimidine derivatives to alkynes has been investigated. The 5,6-double bond of these heterocyclic nuclei has been found to participate in an entirely intermolecular fashion to generate chemo- and stereoselectively novel, fused and substituted 5,6-dihydropyrimidine cobalt complexes, which upon oxidative demetallation liberate the corresponding new heterocyclic ligand. On the other hand, 1-alkynyl pyrimidines have been found to be suitable partners in the cocyclization with disubstituted alkynes, such as bis(trimethylsilyl)acetylene (BTMSA) or dimethyl 2-butyn-1,4-dioate (DMAD), to allow the direct preparation of hitherto unknown dihydropyrido[3,2-ij]quinazoline cobalt complexes. Effects of the substitution on the pyrimidine nucleus, the cocyclization partner, the complex auxiliary, and the reaction conditions were examined, and in some cases competing pathways that lead to [CpCo(cyclobutadienes) ], cyclopentadienone complexes, and compounds that arise from a C-H activation-type reaction were observed.

  DOI：

  10.1002/(sici)1521-3765(19991203)5:12<3549::aid-chem3549>3.0.co;2-v

文献信息

• A Click Chemistry Approach to Pleuromutilin Conjugates with Nucleosides or Acyclic Nucleoside Derivatives and Their Binding to the Bacterial Ribosome
  作者：Line Lolk、Jacob Pøhlsgaard、Anne Sofie Jepsen、Lykke H. Hansen、Henrik Nielsen、Signe I. Steffansen、Laura Sparving、Annette B. Nielsen、Birte Vester、Poul Nielsen

  DOI：10.1021/jm800261u

  日期：2008.8.1

  Pleuromutilin and its derivatives are antibacterial drugs that inhibit protein synthesis in bacteria by binding to ribosomes. To promote rational design of pleuromutilin based drugs, 19 pleuromutilin conjugates with different nucleoside fragments as side chain extensions were synthesized by a click chemistry protocol. Binding was assessed by chemical footprinting of nucleotide U2506 in 23S rRNA, and

  截短侧耳素及其衍生物是通过与核糖体结合而抑制细菌中蛋白质合成的抗菌药物。为了促进基于截短侧耳素的药物的合理设计，通过点击化学方案合成了19种截短侧耳素作为侧链延伸的截短侧耳素缀合物。通过23S rRNA中核苷酸U2506的化学足迹评估结合，所有结合物均以不同程度结合，反映了其与肽基转移酶中心的结合亲和力。侧链延伸部分还在位置U2585处显示了各种保护。对具有最高亲和力的结合物的对接研究支持以下结论：尽管存在各种结合，截短侧耳素骨架仍在相同的结合袋中结合。共轭三唑部分的位置很好，核碱基位于50S核糖体亚基的不同口袋中。与截短侧耳素本身相比，具有最高亲和力和明显更好结合的衍生物包含与截短侧耳素C-22的腺嘌呤9-基丙烯三唑缀合物。
• Cobalt-Mediated [2+2+2] Cycloadditions of Pyrimidine Derivatives to Alkynes
  作者：Hélène Pelissier、Jean Rodriguez、K. Peter C. Vollhardt

  DOI：10.1002/(sici)1521-3765(19991203)5:12<3549::aid-chem3549>3.0.co;2-v

  日期：1999.12.3

  The scope and limitations of the cobalt-mediated [2+2+2] cycloaddition of pyrimidine derivatives to alkynes has been investigated. The 5,6-double bond of these heterocyclic nuclei has been found to participate in an entirely intermolecular fashion to generate chemo- and stereoselectively novel, fused and substituted 5,6-dihydropyrimidine cobalt complexes, which upon oxidative demetallation liberate the corresponding new heterocyclic ligand. On the other hand, 1-alkynyl pyrimidines have been found to be suitable partners in the cocyclization with disubstituted alkynes, such as bis(trimethylsilyl)acetylene (BTMSA) or dimethyl 2-butyn-1,4-dioate (DMAD), to allow the direct preparation of hitherto unknown dihydropyrido[3,2-ij]quinazoline cobalt complexes. Effects of the substitution on the pyrimidine nucleus, the cocyclization partner, the complex auxiliary, and the reaction conditions were examined, and in some cases competing pathways that lead to [CpCo(cyclobutadienes) ], cyclopentadienone complexes, and compounds that arise from a C-H activation-type reaction were observed.
• Flexible double-headed cytosine-linked 2′-deoxycytidine nucleotides. Synthesis, polymerase incorporation to DNA and interaction with DNA methyltransferases
  作者：Pavel Kielkowski、Hana Cahová、Radek Pohl、Michal Hocek

  DOI：10.1016/j.bmc.2016.01.057

  日期：2016.3

  5-iodo-dCTP with the corresponding (fluoro)cytosine-alkynes. The modified dCXCTPs were good substrates for DNA polymerases and were used for enzymatic synthesis of cytosine-functionalized DNA by primer extension or PCR. The cytosine- or fluorocytosine-linked DNA probes did not significantly inhibit DNA methyltransferases and did not cross-link to these proteins.

  新型的双头2'-脱氧胞苷5'- O-三磷酸酯（dC XC TP s）带有另一个通过柔性炔丙基，高炔丙基或戊-1-炔基连接至位置5的胞嘧啶或5-氟胞嘧啶，其制备方法如下： 5-碘-dCTP与相应的（氟）胞嘧啶炔烃的Sonogashira水溶液的交叉偶联反应。修饰的dC XC TP s是DNA聚合酶的良好底物，可用于通过引物延伸或PCR酶法合成胞嘧啶官能化的DNA。胞嘧啶或氟胞嘧啶连接的DNA探针没有明显抑制DNA甲基转移酶，也没有与这些蛋白质交联。