5-azidomethyl-3',5',di-O-acetylthymidine | 72274-20-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-azidomethyl-3',5',di-O-acetylthymidine
• 英文别名: 3′,5′-di-O-acetyl-5-azidomethyl-2′-deoxyuridine；5-azidomethyl-3′,5′-di-O-acetylthymidine；5-(azidomethyl)-2'-deoxy-3',5'-di-O-acetyluridine；5-(azidomethyl)-3',5'-di-O-acetyl-2'-deoxyuridine；3',5'-bis-O-acetyl-5-azidomethyl-2'-deoxyuridine；3',5'-di-O-acetyl-2'-deoxy-5-azidomethyluridine
• CAS: 72274-20-5
• 化学式: C₁₄H₁₇N₅O₇
• 分子量: 367.318
• InChiKey: QTRPQPLUBLRDKN-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.13
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  165.45
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5-azidomethyl-3',5',di-O-acetylthymidine 在 copper(ll) sulfate pentahydrate 、 氨 、 水 、 sodium ascorbate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 38.0h， 生成 5-[(4-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine
  参考文献：
  名称：

  Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides

  摘要：

  Two sets of pyrimidine nucleoside derivatives bearing extended alkyloxymethyl or alkyltriazolidomethyl substituents at position 5 of the nucleobase were synthesized and evaluated as potential antituberculosis agents. The impact of modifications at 3'- and 5'-positions of the carbohydrate moiety on the antimycobacterial activity and cytotoxicity was studied. The highest effect was shown for 5-dodecyloxymethyl-2'-deoxyuridine, 5-decyltriazolidomethyl-2'-deoxyuridine, and 5-dodecyltriazolidomethyl-2'-deoxycytidine. They effectively inhibited the growth of two Mycobacterium tuberculosis strains in vitro, laboratory H37Rv (MIC99 = 20, 10, and 20 mu g/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (MIC99 = 50, 10, and 10 mu g/mL, respectively). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.003
• 作为产物：
  描述：

  5-hydroxymethylene-3',5'-di-O-acetyl-2'-desoxyuridine 在 三甲基氯硅烷 、 sodium azide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 以83 %的产率得到5-azidomethyl-3',5',di-O-acetylthymidine
  参考文献：
  名称：

  5-羟甲基嘧啶核苷的制备：重新研究

  摘要：

  重新研究了目前用于将 5-羟​​甲基部分引入到基于嘧啶的脱氧核苷上的不同方法。胸苷甲基的氧化随后所得甲酰基的还原使得能够以简单的方式并以良好的产率获得受保护的5-羟甲基-2'-脱氧尿苷。给出了相关构建模块合成的应用示例。

  DOI：

  10.1002/ejoc.202300298

文献信息

• Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA, and 2′-Amino-LNA Monomers
  作者：Annika Ries、Rajesh Kumar、Chenguang Lou、Tamer Kosbar、Empar Vengut-Climent、Per T. Jørgensen、Juan C. Morales、Jesper Wengel

  DOI：10.1021/acs.joc.6b01917

  日期：2016.11.18

  thymidine, LNA-T, and 2′-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2′-functionalized 2′-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements

  合成半乳糖修饰的胸苷，LNA-T和2'-氨基-LNA-T核苷，将其转化为相应的亚磷酰胺衍生物，并引入短的寡核苷酸中。与未修饰的对照链相比，一般而言，半乳糖修饰的寡核苷酸，尤其是N2'-官能化的2'-氨基-LNA衍生物，对DNA和RNA补体的双链热稳定性提高，并且能够识别错配。此外，2'-氨基-LNA-T衍生物诱导了显着的3'-核酸外切酶抗性。使用分子模型研究进一步研究了这些结果。
• 5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine as inhibitors of viral and bacterial growth
  作者：L. A. Alexandrova、O. V. Efremenkova、V. L. Andronova、G. A. Galegov、P. N. Solyev、I. L. Karpenko、S. N. Kochetkov

  DOI：10.1134/s1068162016050022

  日期：2016.11

  A series of 5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine have been synthesized by the interaction of 3′,5′-diacetyl-5-azidomethyl-2′-deoxyuridine with the corresponding 1-alkynes in a biphasic methylene chloride—water system catalyzed by Cu(I) followed by the deblocking with a water-alcohol ammonia solution. A low cytotoxicity of the compounds in Vero, Jurkat, and A549 cell cultures

  通过3',5'-二乙酰-5-叠氮甲基-2'的相互作用合成了一系列2'-脱氧尿苷的5-(4-烷基-1,2,3-三唑-1-基)甲基衍生物-脱氧尿苷与相应的 1-炔烃在双相二氯甲烷 - 水系统中由 Cu(I) 催化，然后用水 - 醇氨溶液解封。已显示这些化合物在 Vero、Jurkat 和 A549 细胞培养物中的低细胞毒性。2'-脱氧尿苷衍生物在体外对人类单纯疱疹病毒 1 型 (HSV-1) 的两种实验室毒株表现出抗疱疹活性：阿昔洛韦敏感 (HSV-1/L2) 和阿昔洛韦耐药 (HSV-1/L2RACV) . 它们还在体外抑制了一些细菌（耻垢分枝杆菌、金黄色葡萄球菌、藤黄微球菌和肠系膜明串珠菌）和酵母酿酒酵母的生长。
• Oxygen Independent DNA Interstrand Cross-Link Formation by a Nucleotide Radical
  作者：In Seok Hong、Hui Ding、Marc M. Greenberg

  DOI：10.1021/ja0563657

  日期：2006.1.1

  is the first example of a DNA radical that forms interstrand cross-links. Oxygen labeling experiments support generation of 1 by all precursors. Interstrand cross-links are produced upon irradiation of DNA containing any of the precursors. Cross-linking occurs via reaction with the opposing 2'-deoxyadenosine and is independent of O(2). The independence of cross-link formation on O(2) is explained by

  5-(2'-Deoxyuridinyl)methyl 自由基 (1) 是由三种光化学前体独立产生的，是形成链间交联的 DNA 自由基的第一个例子。氧标记实验支持所有前体产生 1。链间交联是在辐照含有任何前体的 DNA 时产生的。交联通过与相反的 2'-脱氧腺苷反应发生，并且与 O(2) 无关。O(2) 上交联形成的独立性通过动力学分析来解释，这表明自由基与 O(2) 发生可逆反应。检查谷胱甘肽在厌氧条件下对交联形成的影响表明，采用 1 的同步构象是该过程中的限速步骤。在良好亲核试剂的存在下，链间交联的形成是可逆的。链间交联的稳定性表明分离的分子是溶液中形成的重排产物。重排是分离过程的结果，但也在溶液中缓慢发生。不依赖于氧的交联形成可能有助于有目的地破坏缺氧肿瘤细胞中的 DNA，其中 O(2) 不足。
• Synthesis and biological activities of 5-(hydroxymethyl, azidomethyl, or aminomethyl)-2'-deoxyuridine and related 5'-substituted analogs
  作者：George T. Shiau、Raymond F. Schinazi、Ming S. Chen、William H. Prusoff

  DOI：10.1021/jm00176a005

  日期：1980.2

  hydrogenation of the azides 9, 10, 14, and 15 gave the corresponding amines 16, 2, 6, and 7, respectively. Compounds 1, 2, 10, and 16 inhibited the growth of murine Sarcoma 180 and L1210 in culture, and the activity of 2 was prevented by 2'-deoxypyrimidine nucleosides but not by purine nucleosides. The replication of herpes simplex virus type 1 (HSV-1) was strongly inhibited only by 1 and 10. Studies on the

  5-（叠氮甲基）-2′-脱氧尿苷（10）的合成已通过两种独立的方法完成。首先涉及5-（羟甲基）-2'-脱氧尿苷的甲苯磺酸化（1），以提供两种单-和二甲苯基核苷的混合物，将其转化为相应的5-（叠氮甲基）（10），5-（叠氮甲基） 2′-脱氧尿苷的-5′-叠氮基（14）和5-（羟甲基）-5′-叠氮基（15）衍生物。第二种方法更具选择性，需要形成中间体5-（溴甲基）-3'，5'-二-O-乙酰基-2'-脱氧尿苷（8），然后用叠氮化锂和溴化取代溴基。脱乙酰。叠氮化物9、10、14和15的催化氢化分别得到相应的胺16、2、6和7。化合物1、2、10和16抑制了培养物中鼠肉瘤180和L1210的生长，2'的活性被2'-脱氧嘧啶核苷阻止，但嘌呤核苷阻止。1型单纯疱疹病毒（HSV-1）的复制仅受到1和10的强烈抑制。对各种胸苷类似物与HSV-1编码的嘧啶脱氧核糖核苷激酶结合的研究表明1和10对这种酶具有良好的亲和力。
• Design, Synthesis, and Antiviral Evaluation of Chimeric Inhibitors of HIV Reverse Transcriptase
  作者：Pinar Iyidogan、Todd J. Sullivan、Mahendra D. Chordia、Kathleen M. Frey、Karen S. Anderson

  DOI：10.1021/ml4002979

  日期：2013.12.12

  In a continuing study of potent bifunctional anti-HIV agents, we rationally designed a novel chimeric inhibitor utilizing thymidine (THY) and a TMC derivative (a diarylpyrimidine NNRTI) linked via a polymethylene linker (ALK). The nucleoside, 5'-hydrogen-phosphonate (H-phosphonate), and S'-triphosphate forms of this chimeric inhibitor (THY-ALK-TMC) were synthesized and the antiviral activity profiles were evaluated at the enzyme and cellular level. The nucleoside triphosphate (11) and the H-phosphonate (10) derivatives inhibited RT polymerization with an IC50 value of 6.0 and 4.3 nM, respectively. Additionally, chimeric nucleoside (9) and H-phosphonate (10) derivatives reduced HIV replication in a cell-based assay with low nanomolar antiviral potencies.