3',5'-bis-O-(trimethylsilyl)-thymidine | 10457-18-8

• 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',5'-bis-O-(trimethylsilyl)-thymidine
• 英文别名: 3',5'-O-bis-(trimethylsilyl)-thymidine；bis(trimethylsilyl)thymidine；O-bis-3',5'(trimthylsilyl)thymidin；O^3'_,O5'-bis-trimethylsilanyl-thymidine；TMS(-3)[TMS(-5)]2-deoxy-D-eryPenf(b)-thymin-1-yl；5-methyl-1-[(2R,4S,5R)-4-trimethylsilyloxy-5-(trimethylsilyloxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 10457-18-8
• 化学式: C₁₆H₃₀N₂O₅Si₂
• 分子量: 386.596
• InChiKey: IIORRTMASMPHAF-BFHYXJOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3',5'-bis-O-(trimethylsilyl)-thymidine 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 beta-胸苷
  参考文献：
  名称：

  Selective alkylation of pyrimidyl dianions II: synthesis, characterization, and comparative reactivity of 3′, 5′-o-bis- tetrahydropyranyl, trimethylsilyl and tert-butyldimethylsilyl derivatives of 5-bromo-2′-deoxyuridine

  摘要：

  Three compounds which can be used as precursors for thymidine synthesis via methylation at the 5 position, including 3', 5'-o-bis(tetrahydropyranyl)-5-bromo-2'-deoxyuridine 1a, 3', 5'-o-bis-(trimethylsily)-5-bromo-2'-deoxyuridine 1b, and 3', 5'-o-bis-(t-butyldimethylsilyl)-5-bromo-2'-deoxyuridine 1c, were prepared isolated and characterized by spectroscopic methods. Alkylation with methyl iodide using an organo-lithium reagent at low temperature produced 72%, 41% and 74% of thymidine 6, respectively. Tetrahydropyranyl and t-butyldimethylsilyl ethers are found to be better precursors for introduction of a methyl group at the 5 position.

  DOI：

  10.1016/s0040-4020(01)80845-0
• 作为产物：
  描述：

  溴脲苷 在 正丁基锂 、 TEA 、 碘甲烷 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.5h， 生成 3',5'-bis-O-(trimethylsilyl)-thymidine
  参考文献：
  名称：

  Selective alkylation of pyrimidyl dianions II: synthesis, characterization, and comparative reactivity of 3′, 5′-o-bis- tetrahydropyranyl, trimethylsilyl and tert-butyldimethylsilyl derivatives of 5-bromo-2′-deoxyuridine

  摘要：

  Three compounds which can be used as precursors for thymidine synthesis via methylation at the 5 position, including 3', 5'-o-bis(tetrahydropyranyl)-5-bromo-2'-deoxyuridine 1a, 3', 5'-o-bis-(trimethylsily)-5-bromo-2'-deoxyuridine 1b, and 3', 5'-o-bis-(t-butyldimethylsilyl)-5-bromo-2'-deoxyuridine 1c, were prepared isolated and characterized by spectroscopic methods. Alkylation with methyl iodide using an organo-lithium reagent at low temperature produced 72%, 41% and 74% of thymidine 6, respectively. Tetrahydropyranyl and t-butyldimethylsilyl ethers are found to be better precursors for introduction of a methyl group at the 5 position.

  DOI：

  10.1016/s0040-4020(01)80845-0

文献信息

• NMR and UV Studies of 4-Thio-2′-deoxyuridine and Its Derivatives
  作者：Xiaohui Zhang、Yao-Zhong Xu

  DOI：10.3390/molecules16075655

  日期：——

  5-Substituted-4-thio-2'-deoxyuridine nucleosides have been chemically synthesized and studied by NMR and UV spectroscopy. The results have been analyzed and discussed in connection with the previous data. The imino proton signal and the carbon signal of the thiocarbonyl group in the 5-substituted-4-thio-2'-deoxyuridines were found to be at much lower field, offering a potential for monitoring these

  5-Substituted-4-thio-2'-deoxyuridine nucleosides 已被化学合成并通过 NMR 和 UV 光谱进行了研究。已经结合先前的数据对结果进行了分析和讨论。发现 5-取代-4-硫代-2'-脱氧尿苷中的亚氨基质子信号和硫代羰基的碳信号处于低得多的场中，为在 DNA 水平上监测这些修饰碱基提供了潜力。所有 4-硫代核苷在 340 nm 附近都有很强的吸收，因此可用作潜在的 UVA 诱导的抗癌剂。
• Synthesis of Oligodeoxynucleotides Using Fully Protected Deoxynucleoside 3′-Phosphoramidite Building Blocks and Base Recognition of Oligodeoxynucleotides Incorporating N3-Cyano-Ethylthymine
  作者：Hirosuke Tsunoda、Tomomi Kudo、Akihiro Ohkubo、Kohji Seio、Mitsuo Sekine

  DOI：10.3390/molecules15117509

  日期：——

  Oligodeoxynucleotide (ODN) synthesis, which avoids the formation of side products, is of great importance to biochemistry-based technology development. One side reaction of ODN synthesis is the cyanoethylation of the nucleobases. We suppressed this reaction by synthesizing ODNs using fully protected deoxynucleoside 3'-phosphoramidite building blocks, where the remaining reactive nucleobase residues

  寡聚脱氧核苷酸 (ODN) 合成避免了副产物的形成，对于基于生物化学的技术开发具有重要意义。ODN 合成的一个副反应是核碱基的氰乙基化。我们通过使用完全受保护的脱氧核苷 3'-亚磷酰胺结构单元合成 ODN 来抑制该反应，其中剩余的反应性核碱基残基被酰基-、二酰基-和酰基-氧乙烯型基团完全保护。对核碱基位点氰乙基化的详细分析表明，胸腺嘧啶碱基的 N3 保护有效地抑制了丙烯腈的迈克尔加成。使用亚磷酰胺方法合成了包含 N3-氰乙基胸腺嘧啶的 ODN，并检查了涉及该 ODN 模板的引物延伸反应。其结果，
• Synthesis of 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as a model compound for evaluation of cyanoethyl cleavage
  作者：Angelika C. Keller、Saulius Serva、Diana C. Knapp、Marek Kwiatkowski、Joachim W. Engels

  DOI：10.1135/cccc2008183

  日期：——

  An essential and challenging task during the development of our sequencing-by-synthesis (SBS) technique is the evaluation of efficient cyanoethyl (CE) cleavage conditions. For this purpose 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as a model compound as well as a short DNA oligomer bearing the CE function as terminal group were synthesized and used for various deprotection experiments. As it is already known for 2′-O-CE-protected RNA oligonucleotides, the CE function can be cleaved with tetrabutylammonium fluoride (TBAF) in THF. Indeed, by using 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as a simple model compound for cleavage tests, we found out that the 3′-O-CE function is quantitatively cleaved with 1 M TBAF in THF. However, the CE group is also cleaved by other small bases like hydroxy groups under alkaline conditions. The CE cleavage with TBAF in THF gives the fastest and quantitative removal of the CE group under mild conditions for our sequencing-by-synthesis (SBS) application. The efficient removal of the 3′-CE group is crucial for the proof-of-principle of our SBS approach using dye-labeled 3′-CE-blocked dNTPs, which is currently under investigation. Herein we describe the application of 3′-O-(2-cyanoethyl)-2′-deoxythymidine-5′-phosphate as model compound for the development of reversible terminators for the SBS technique. Furthermore we suggest that nucleoside phosphates bearing any removable 3′-modification might be suitable model compounds for cleavage studies in a heterogeneous environment comparable to an oligonucleotide/ aprotic solvent system.

  在我们的合成-通过合成（SBS）技术开发过程中，一个重要且具有挑战性的任务是评估高效的氰乙基（CE）裂解条件。为此，我们合成了3'-O-(2-氰乙基)-2'-脱氧胸苷-5'-磷酸作为模型化合物，以及一个带有CE功能作为末端基团的短DNA寡聚体，并用于各种去保护实验。正如已经知道的对于2'-O-CE-保护的RNA寡核苷酸，CE功能可通过THF中的四丁基氟化铵（TBAF）来裂解。事实上，通过使用3'-O-(2-氰乙基)-2'-脱氧胸苷-5'-磷酸作为裂解试验的简单模型化合物，我们发现3'-O-CE功能在1 M TBAF/THF条件下可以被完全裂解。然而，CE基团也会在碱性条件下被其他小碱基如羟基裂解。在我们的合成-通过合成（SBS）应用中，CE裂解与TBAF/THF在温和条件下提供了最快和定量的CE基团去除。对3'-CE基团的高效去除对于使用染料标记的3'-CE阻断的dNTPs进行SBS方法的原理证明至关重要，目前正在进行研究。在这里，我们描述了3'-O-(2-氰乙基)-2'-脱氧胸苷-5'-磷酸作为合成-通过合成（SBS）技术的可逆终止子的开发的模型化合物的应用。此外，我们建议带有任何可去除的3'-修饰的核苷酸磷酸盐可能是适合的模型化合物，用于在类似寡核苷酸/无极性溶剂体系中进行裂解研究。
• An Improved Method for the Synthesis of<i>N</i> ³-Benzoylthymidine
  作者：Mitsuo Sekine、Mitsuo Fujii、Hajime Nagai、Tsujiaki Hata

  DOI：10.1055/s-1987-28192

  日期：——

  N 3-Benzoylthymidine (2), a key intermediate for oligodeoxyribonucleotide synthesis, was synthesized in high yield via 3′, 5′-bis-O-(trimethylsilyl)-N 3-benzoylthymidine, which could be isolated as stable crystals.

  通过 3′，5′-双-O-（三甲基硅基）-N 3-苯甲酰基胸苷，高产合成了寡脱氧核苷酸合成的关键中间体 N 3-苯甲酰基胸苷（2），并可将其分离为稳定的晶体。
• BASE-PROTECTED OLIGONUCLEOTIDE
  申请人：AJINOMOTO CO., INC.

  公开号：EP2816053B1

  公开（公告）日：2021-03-24