3-(2-bromoethyl)-1-((2R,4S,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione | 1058159-38-8

• 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: 3-(2-bromoethyl)-1-((2R,4S,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 3-(2-bromoethyl)-3',5'-di-O-(tert-butyl-dimethyl-silanyl)thymidine；3-(2-bromoethyl)-3',5'-bis-O-(tert-butyldimethylsilanyl)thymidine；3-(2-bromoethyl)-1-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1058159-38-8
• 化学式: C₂₄H₄₅BrN₂O₅Si₂
• 分子量: 577.707
• InChiKey: WGNGNTXNZNKRFO-XUVXKRRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  68.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-bromoethyl)-1-((2R,4S,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione 在 sodium azide 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以80%的产率得到3-(2-azidoethyl)-1-((2R,4S,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H, 3H)-dione
  参考文献：
  名称：

  “点击螯合剂”：设计和将含三唑的金属螯合系统并入具有诊断和治疗意义的生物分子中。

  摘要：

  金属螯合系统与生物学相关分子的位点特异性缀合是生物无机和生物有机金属化学中的重要当代课题。在这项工作中，我们已经使用了CuI催化的叠氮化物和末端炔烃的环加成反应合成新的配体系统，其中1,2,3-三唑是金属螯合系统的组成部分。制备了一组具有不同脂族和芳族主链以及各种供体基团的二齿双炔结构单元。在催化量的CuI存在下，使二齿炔与苄基叠氮化物反应以形成三齿模型配体。螯合剂与[ReBr3（CO）3] 2-反应形成具有不同总体电荷，结构和亲水性的定义明确且稳定的络合物。在所有情况下，配体的三齿配位，观察到包括通过N 3的1,2,3-三唑环。配体系统也可以在低配体浓度下用前体[99 mTc（H2O）3（CO）3] +进行放射性同位素标记。类似地，炔烃与叠氮胸腺嘧啶核苷衍生物反应形成一系列化合物，可以对其进行原位放射性标记以形成单一产物。随后将中性和阳离子型有机金属99 mTc胸腺嘧啶核苷衍生物与人胞质

  DOI：

  10.1002/chem.200702024
• 作为产物：
  描述：

  1,2-二溴乙烷 、 3,5-双-o-(t-丁基二甲基甲硅烷基)胸腺嘧啶脱氧核苷 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 以95%的产率得到3-(2-bromoethyl)-1-((2R,4S,5R)-4-((tert-butyldimethylsilyl)oxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  “点击螯合剂”：设计和将含三唑的金属螯合系统并入具有诊断和治疗意义的生物分子中。

  摘要：

  金属螯合系统与生物学相关分子的位点特异性缀合是生物无机和生物有机金属化学中的重要当代课题。在这项工作中，我们已经使用了CuI催化的叠氮化物和末端炔烃的环加成反应合成新的配体系统，其中1,2,3-三唑是金属螯合系统的组成部分。制备了一组具有不同脂族和芳族主链以及各种供体基团的二齿双炔结构单元。在催化量的CuI存在下，使二齿炔与苄基叠氮化物反应以形成三齿模型配体。螯合剂与[ReBr3（CO）3] 2-反应形成具有不同总体电荷，结构和亲水性的定义明确且稳定的络合物。在所有情况下，配体的三齿配位，观察到包括通过N 3的1,2,3-三唑环。配体系统也可以在低配体浓度下用前体[99 mTc（H2O）3（CO）3] +进行放射性同位素标记。类似地，炔烃与叠氮胸腺嘧啶核苷衍生物反应形成一系列化合物，可以对其进行原位放射性标记以形成单一产物。随后将中性和阳离子型有机金属99 mTc胸腺嘧啶核苷衍生物与人胞质

  DOI：

  10.1002/chem.200702024

文献信息

• Synthesis and Biological Evaluation of Novel 99mTc(CO)3-Labeled Thymidine Analogs as Potential Probes for Tumor Proliferation Imaging
  作者：Xiaojiang Duan、Teli Liu、Yichun Zhang、Junbo Zhang

  DOI：10.3390/molecules21040510

  日期：——

  Achieving a (99m)Tc labeled thymidine radiotracer for single photon emission tomography (SPECT) is considered to be of interest. In this study, four novel thymidine analogs, 6a, 6b, 6c and 6d, were successfully synthesized via "click reaction" route and then radiolabeled using a [(99m)Tc(CO)₃]⁺ core to prepare the corresponding (99m)Tc(CO)₃ complexes in high yields. These complexes were hydrophilic

  实现单光子发射断层扫描（SPECT）的（99m）Tc标记的胸苷放射性示踪剂被认为是令人感兴趣的。在这项研究中，成功​​地通过“点击反应”路线合成了四个新颖的​​胸苷类似物6a，6b，6c和6d，然后使用[（99m）Tc（CO）₃]⁺核进行了放射性标记，制备了相应的（99m） Tc（CO）₃络合物产率高。这些复合物是亲水的，并具有良好的体外稳定性。这些复合物在患有S180肿瘤的小鼠中的生物分布表明，它们均在肿瘤中表现出蓄积，表明它们将是潜在的肿瘤显像剂。
• Synthesis, In Vitro, and In Silico Evaluation of Organometallic Technetium and Rhenium Thymidine Complexes with Retained Substrate Activity toward Human Thymidine Kinase Type 1
  作者：Dominique Desbouis、Harriet Struthers、Vojtech Spiwok、Tatiana Küster、Roger Schibli

  DOI：10.1021/jm800530p

  日期：2008.11.13

  Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for noninvasive imaging of cancer cell proliferation using radiolabeled substrates such as [F-18]fluorothymidine ([F-18]FLT). However, a thymidine tracer useful for single photon emission tomography (SPECT) based off the inexpensive radionuclide technetium-99m would be of significant interest. In this work, a series of thymidine derivatives labeled with the organometallic [M(CO)(3)](+) core (M = Tc-99m, Re) were synthesized. Neutral, cationic, and anionic complexes were readily formed in aqueous media. and all were substrates of recombinant hTK1 when incubated with ATP. The neutral complexes were phosphorylated to a greater extent than the charged complexes. The extent of phosphorylation was further improved by increasing the spacer length separating thymidine and the organometallic core. A molecular dynamics Simulation Study performed with a modified hTK1 structure Supported the experimental findings. In vitro cell internalization experiments performed if) a human neuroblastoma cell line (SKNMC) showed low uptake of the charged complexes but significant uptake for the neutral, lipophilic complexes with a log P value > 1.
• Charge Dependent Substrate Activity of C3′ and N3 Functionalized, Organometallic Technetium and Rhenium-Labeled Thymidine Derivatives toward Human Thymidine Kinase 1
  作者：Harriet Struthers、David Viertl、Marek Kosinski、Bernhard Spingler、Franz Buchegger、Roger Schibli

  DOI：10.1021/bc900380n

  日期：2010.4.21

  Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for the noninvasive imaging of cancer cell proliferation using radiolabeled thymidine analogues such as [(18)F]3'-fluoro-3'-deoxythymidine ([(18)F]FLT). A thymidine analogue for single photon emission computed tomography (SPECT), which incorporates the readily available and inexpensive nuclide technetium-99m, would be of considerable practical interest. hTK1 is known to accommodate modification of the structure of the natural substrate thymidine at the positions N3 and C3' and, to a lesser extent, C5. In this work, we used the copper-catalyzed azide-alkyne cycloaddition to synthesize two series of derivatives in which thymidine is functionalized at either the C3' or N3 position with chelating systems suitable for the M(CO)(3) core (M = (99m)Tc, Re). The click chemistry approach enabled complexes with different structures and overall charges to he synthesized from a common precursor. Using this strategy, the first organometallic hTK1 substrates in which thymidine is modified at the C3' position were identified. Phosphorylation of the organometallic derivatives was measured relative to thymidine. We have shown that the influence of the overall charge of the derivatives is dependent on the position of functionalization. In the case of the C3'-functionalized derivatives, neutral and anionic substrates were most readily phosphorylated (20-28% of the value for the parent ligand thymidine), whereas for the N3-functionalized derivatives, cationic and neutral complexes were apparently better substrates for the enzyme (14-18%) than anionic derivatives (9%).
• “Click‐to‐Chelate”: Design and Incorporation of Triazole‐Containing Metal‐Chelating Systems into Biomolecules of Diagnostic and Therapeutic Interest
  作者：Harriet Struthers、Bernhard Spingler、Thomas L. Mindt、Roger Schibli

  DOI：10.1002/chem.200702024

  日期：2008.7.7

  site-specific conjugation of metal chelating systems to biologically relevant molecules is an important contemporary topic in bioinorganic and bioorganometallic chemistry. In this work, we have used the CuI-catalyzed cycloaddition of azides and terminal alkynes to synthesise novel ligand systems, in which the 1,2,3-triazole is an integral part of the metal chelating system. A diverse set of bidentate alkyne

  金属螯合系统与生物学相关分子的位点特异性缀合是生物无机和生物有机金属化学中的重要当代课题。在这项工作中，我们已经使用了CuI催化的叠氮化物和末端炔烃的环加成反应合成新的配体系统，其中1,2,3-三唑是金属螯合系统的组成部分。制备了一组具有不同脂族和芳族主链以及各种供体基团的二齿双炔结构单元。在催化量的CuI存在下，使二齿炔与苄基叠氮化物反应以形成三齿模型配体。螯合剂与[ReBr3（CO）3] 2-反应形成具有不同总体电荷，结构和亲水性的定义明确且稳定的络合物。在所有情况下，配体的三齿配位，观察到包括通过N 3的1,2,3-三唑环。配体系统也可以在低配体浓度下用前体[99 mTc（H2O）3（CO）3] +进行放射性同位素标记。类似地，炔烃与叠氮胸腺嘧啶核苷衍生物反应形成一系列化合物，可以对其进行原位放射性标记以形成单一产物。随后将中性和阳离子型有机金属99 mTc胸腺嘧啶核苷衍生物与人胞质