3'-O-acetyl-5'-azido-5'-deoxythymidine | 27766-92-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 2 '，5'-二脱氧核苷
• 英文名称: 3'-O-acetyl-5'-azido-5'-deoxythymidine
• 英文别名: [(2R,3S,5R)-2-(azidomethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] acetate
• CAS: 27766-92-3
• 化学式: C₁₂H₁₅N₅O₅
• 分子量: 309.282
• InChiKey: WSGCZIPIFONUNE-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3'-O-acetyl-5'-azido-5'-deoxythymidine 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 5-叠氮基-5-脱氧胸腺嘧啶脱氧核苷
  参考文献：
  名称：

  5'-Azido and 5'-Fluoro alpha-Nucleosides as Analogues of AZT and FLT.

  摘要：

  5-Azido-2,5-dideoxy-beta-D-erythro-pentofuranosyl nucleosides 10 and their corresponding alpha-anomers 11 have been synthesized by condensation of methyl 3-O-acetyl-5-azido-2,5-dideoxy-beta-D-erythro-pentofuranoside (7) with silylated nucleobases followed by deprotection with methanolic ammonia. Reaction of silylated thymine (19) with methyl 2,3-di-O-benzoyl-5-deoxy-5-fluoro-D-arabino-pentofuranoside (15) and methyl 5-azido-2,3-di-O-benzoyl-5-deoxy-alpha-D-arabino-pentofuranoside (17alpha) afforded a mixture of the alpha-nucleosides 20 and the acyclo nucleosides 5-fluoro- and 5-azido-2,3-O-dibenzoyl-5-deoxy-1-O-methyl-1-(thymin-1-yl)-D-arabinitol (22). Compounds 20 and 22 were deprotected with methanolic ammonia to give the acyclic nucleosides 21 and 23, respectively. The new nucleosides were inactive against HSV-1 and HIV-1.

  DOI：

  10.3891/acta.chem.scand.48-0215
• 作为产物：
  描述：

  3'-O-acetylthymidine 在 吡啶 、 sodium azide 、 lithium bromide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 3'-O-acetyl-5'-azido-5'-deoxythymidine
  参考文献：
  名称：

  三唑基13α-雌激素-核苷生物共轭物的合成及生物学评价。

  摘要：

  通过应用铜催化的炔-叠氮化物点击反应（CuAAC）合成了13α-雌酮的2'-脱氧核苷共轭物。为了引入叠氮基，选择了核苷的5'-位和13α-雌酮的3-羟基上的炔丙基醚官能团。当核苷的3'-羟基被乙酰基保护并且5'-羟基通过甲苯磺酰叠氮化物交换法进行修饰时，我们的手中获得了最佳收率。受保护的5'-叠氮核苷和甾类炔烃之间单击反应的常用条件通过使用1.5当量的Cu（I）催化剂进行了轻微修饰。所有制备的缀合物均通过MTT分析法在体外评估，其针对一组人类粘附细胞系（HeLa，通过体外放射性底物孵育研究了MCF-7和A2780）以及新缀合物对人17β-羟基类固醇脱氢酶1（17β-HSD1）的潜在抑制活性。一些受保护的缀合物对一组人类粘附癌细胞系表现出中等的抗增殖特性（受保护的胞苷缀合物被证明是最有效的，IC50值为9μM）。胸苷偶联物显示出相当大的17β-HSD1抑制活性（IC50 = 19μM）。一些

  DOI：

  10.3390/molecules21091212

文献信息

• Synthesis and Biological Evaluations of Click-Generated Nitrogen Mustards
  作者：Benjamin Boëns、Tan-Sothea Ouk、Yves Champavier、Rachida Zerrouki

  DOI：10.1080/15257770.2015.1017580

  日期：2015.7.3

  This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological

  本文介绍了新型点击产生的氮芥的合成及其生物学评价。通过使用铜催化的叠氮化物-炔烃环加成（CuAAC）反应，我们设法合成了八种新的氮芥。该策略为合成具有重要结构变异性的新氮芥家族奠定了基础。此外，我们通过测试合成化合物对四种代表性癌细胞系A431，JURKAT，K562和U266的细胞毒性来研究其生物学活性。一种结构，1-苄基-4-（N，N-二-2-氯乙基氨基甲基）-1H- [ 1 DM，Noll；McG.Mason，T .；Miller，PS 在DNA中形成和修复链间交联。化学 修订2006年，106，277 - 301。[Crossref]，[PubMed]，[Web of Science®]， [Google Scholar]，2 Rink，SM；霍普金斯（Hopkins），PB 直接证据表明合成的寡核苷酸中氮芥芥甲氧乙胺可实现DNA链内交联。Bioorg。中 化学 来吧 1995年，5（23），2845
• 10.1002/cmdc.202400088
  作者：Szabo, Rémi、Dobie, Chris、Montgomery, Andrew P.、Steele, Harrison、Yu, Haibo、Skropeta, Danielle

  DOI：10.1002/cmdc.202400088

  日期：——

  into 1,2,3-triazole linked sialyltransferase inhibitors, we present the design and synthesis of a new series of compounds that improve upon the drug-likeness of the parent scaffold. Additionally, we performed a preliminary SAR study with the STs hST3GAL1, hST6GAL1, and hST8SIA2. This work provides new insights into the design of selective ST inhibitors, particularly considering different nucleoside

  基于我们之前对 1,2,3-三唑连接的唾液酸转移酶抑制剂的研究，我们提出了一系列新化合物的设计和合成，这些化合物改进了母体支架的药物相似性。此外，我们还使用 STs hST3GAL1 、 hST6GAL1 和 hST8SIA2 进行了初步 SAR 研究。这项工作为选择性 ST 抑制剂的设计提供了新的见解，特别是考虑了不同的核苷衍生物。
• Development and characterization of lysine based tripeptide analogues as inhibitors of Sir2 activity
  作者：Subhra Prakash Chakrabarty、Ramesh Ramapanicker、Roli Mishra、Srinivasan Chandrasekaran、Hemalatha Balaram

  DOI：10.1016/j.bmc.2009.10.003

  日期：2009.12

  Sirtuins are NAD(+) dependent deacetylases that modulate various essential cellular functions. Development of peptide based inhibitors of Sir2s would prove useful both as pharmaceutical agents and as effectors by which downstream cellular alterations can be monitored. Click chemistry that utilizes Huisgen's 1,3-dipolar cycloaddition permits attachment of novel modifications onto the side chain of lysine. Herein, we report the synthesis of peptide analogues prepared using click reactions on N epsilon-propargyloxycarbonyl protected lysine residues and their characterization as inhibitors of Plasmodium falciparum Sir2 activity. The peptide based inhibitors exhibited parabolic competitive inhibition with respect to acetylated-peptide substrate and parabolic non-competitive inhibition with NAD(+) supporting the formation of EI2 and E.NAD(+).I-2 complexes. Cross-competition inhibition analysis with the non-competitive inhibitor nicotinamide (NAM) ruled out the possibility of the NAM-binding site being the second inhibitor binding site, suggesting the presence of a unique alternate pocket accommodating the inhibitor. One of these compounds was also found to be a potent inhibitor of the intraerythrocytic growth of P. falciparum with 50% inhibitory concentration in the micromolar range. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of Extended Carbamate and Urea Linked Thymidine Dimers¹
  作者：Shoukath M. Ali、Peter K. Bridson

  DOI：10.1080/07328319608002452

  日期：1996.9

  Thymidine dimers with extended carbamate and urea linkages were-synthesized. The length of the linker is expected to increase flexibility and improve duplex formation after incorporation into oligomer.
• Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates
  作者：Brigitta Bodnár、Erzsébet Mernyák、János Wölfling、Gyula Schneider、Bianka Herman、Mihály Szécsi、Izabella Sinka、István Zupkó、Zoltán Kupihár、Lajos Kovács

  DOI：10.3390/molecules21091212

  日期：——

  alkyne-azide click reaction (CuAAC). For the introduction of the azido group the 5'-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3'-hydroxy groups of the nucleosides were protected by acetyl groups and the 5'-hydroxy groups were modified by the tosyl-azide exchange method. The commonly

  通过应用铜催化的炔-叠氮化物点击反应（CuAAC）合成了13α-雌酮的2'-脱氧核苷共轭物。为了引入叠氮基，选择了核苷的5'-位和13α-雌酮的3-羟基上的炔丙基醚官能团。当核苷的3'-羟基被乙酰基保护并且5'-羟基通过甲苯磺酰叠氮化物交换法进行修饰时，我们的手中获得了最佳收率。受保护的5'-叠氮核苷和甾类炔烃之间单击反应的常用条件通过使用1.5当量的Cu（I）催化剂进行了轻微修饰。所有制备的缀合物均通过MTT分析法在体外评估，其针对一组人类粘附细胞系（HeLa，通过体外放射性底物孵育研究了MCF-7和A2780）以及新缀合物对人17β-羟基类固醇脱氢酶1（17β-HSD1）的潜在抑制活性。一些受保护的缀合物对一组人类粘附癌细胞系表现出中等的抗增殖特性（受保护的胞苷缀合物被证明是最有效的，IC50值为9μM）。胸苷偶联物显示出相当大的17β-HSD1抑制活性（IC50 = 19μM）。一些