3'-O-tritylthymidine | 73189-04-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 3'-O-tritylthymidine
• 英文别名: 1-[(2R,4S,5R)-5-(hydroxymethyl)-4-trityloxy-tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,4S,5R)-5-(hydroxymethyl)-4-trityloxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 73189-04-5
• 化学式: C₂₉H₂₈N₂O₅
• 分子量: 484.552
• InChiKey: ROOKAEQGWFPJLG-JIMJEQGWSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-苄氧基-4-(2-溴乙氧基)苯 、 3'-O-tritylthymidine 在 sodium hydride 作用下， 以 1,4-二氧六环 、 苯 为溶剂， 生成
  参考文献：
  名称：

  重新评估在5'-位带有大基团的胸苷衍生物对胸苷激酶的作用。

  摘要：

  通过化学上稳定的酰胺和醚键连接的具有疏水性5'-取代基的几种胸苷衍生物被合成为潜在的胸苷激酶抑制剂。这些都没有活性，胸腺嘧啶5'-乙酸酯的几种衍生物也没有活性，以前报道它们是抑制剂。结果表明，后一种化合物的明显抑制作用是由于它们在水溶液中易于水解而释放了胸苷。这些结果必须使人们对从5'-胸苷的生物学研究得出的任何结论产生怀疑。

  DOI：

  10.1021/jm00374a018
• 作为产物：
  描述：

  在 水 、 lithium hydroxide 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以61%的产率得到3'-O-tritylthymidine
  参考文献：
  名称：

  In search of flavivirus inhibitors: Evaluation of different tritylated nucleoside analogues

  摘要：

  Following up on a hit that was identified in a large scale cell-based antiviral screening effort, a series of triphenylmethyl alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against the dengue virus (DENV) and the yellow fever virus (YFV). Hereto, trityl moieties were attached at various positions of the sugar ring combined with subtle variations of the heterocyclic base. Several triphenylmethyl modified nucleosides were uncovered being endowed with submicromolar in vitro antiviral activity against the YFV. The most selective inhibitor in this series was 3',5'-bis-O-tritylated-5-chlorouridine (1b) affording a selectivity index of over 90, whereas the 3',5'-bis-O-tritylated inosine congener (5b) displayed the highest activity, but proved more toxic. The finding of these lipophilic structures being endowed with high antiviral activity for flaviviruses, should stimulate the interest for further structure-activity research. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.034

文献信息

• In search of Flavivirus inhibitors part 2: Tritylated, diphenylmethylated and other alkylated nucleoside analogues
  作者：Milind Saudi、Joanna Zmurko、Suzanne Kaptein、Jef Rozenski、Johan Neyts、Arthur Van Aerschot

  DOI：10.1016/j.ejmech.2014.02.011

  日期：2014.4

  hit 3′,5′-bistritylated uridine 1, a series of alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against dengue fever virus and yellow fever virus. Hereto, alkyl and aryl groups were attached at various positions of the sugar ring combined with subtle variation of the heterocyclic base. Among the new series of derivatives, 3′,5′-di-O-trityl-5-fluoro-2′-deoxyuridine

  几种黄病毒，例如黄热病病毒和登革热病毒，会在人体内引起严重的致命感染。继我们最初的命中3'，5'-双歧化尿苷1之后，合成了一系列烷基化核苷类似物，并评估了它们对登革热病毒和黄热病病毒的体外抗病毒活性。迄今为止，烷基和芳基连接在糖环的各个位置，并带有杂环碱基的细微变化。在新的衍生物系列中，3'，5'- di- O-三苯甲基-5-氟-2'-脱氧尿苷（39）是该系列中最有效的衍生物，可抑制黄热病病毒和登革热病毒的复制，其50有效浓度百分比（EC 50）〜1μg/ mL，无明显细胞毒性。其他氟化衍生物被证明更具毒性。几乎所有具有3'，5'-二-O-苯甲酰基-2'-脱氧尿苷（50）的二苯基甲基化嘧啶核苷都具有很强的低至1μg/ mL的细胞毒性作用。
• Protecting Groups Transfer: Unusual Method of Removal of Tr and Tbdms Groups by Transetherification
  作者：Nadia L. D. Cabral、Luciano J. Hoeltgebaum Thiessen、Bogdan Doboszewski

  DOI：10.1080/15257770802257846

  日期：2008.8.11

  The triphenylmethyl (Tr) group undergoes a transfer (transetherification or disproportionation) between the molecules of 5′-O-Tr-2′-deoxynucleosides in a process mediated by anhydrous sulfates of Cu+2, Fe+2, or Ni+2 to yield mixtures of 3′,5′-bis-O-Tr and 3′-O-Tr products. If phenylmethanol is present in a reaction medium, detritylation results with concomitant formation of phenylmethyl triphenylmethyl

  在由Cu + 2，Fe + 2或Ni + 2的无水硫酸盐介导的过程中，三苯甲基（Tr）基团在5'-O-Tr-2'-脱氧核苷分子之间进行转移（转移醚化或歧化）得到3′，5′-双-O-Tr和3′-O-Tr产物的混合物。如果反应介质中存在苯甲醇，则会导致脱三苯甲基化并同时形成苯甲基三苯甲基醚。5'-O-TBDMS-2'-脱氧核苷中叔丁基二甲基甲硅烷基（TBDMS）的行为完全相同。以前没有在O-Tr和O-TBDMS组中观察到这种类型的转醚化作用。
• A short synthesis of 5′-<i>O</i>-trityl-protected<i>threo</i>- and<i>erythro</i>- 3′-cyano-3′-deoxythymidine epimers using free-radical chemistry
  作者：Donald D. Bankston、Merrick R. Almond

  DOI：10.1002/jhet.5570290606

  日期：1992.10

  A reinvestigation of a synthetic route to 5′-O-trityl-protected erythro-CNT that incorporates a modification of the Stork radical cyclization-cyanation reaction generates an unexpected threo-epimer.

  对结合了斯托克自由基环化-氰化反应的修饰的5'- O-三苯甲基保护的赤型-CNT的合成路线的重新研究产生了意外的苏式表位。
• Backbone modified oligonucleotide analogues
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20030045705A1

  公开（公告）日：2003-03-06

  Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

  提供了具有改进核酸酶抗性和改进细胞摄取能力的治疗性寡核苷酸类似物。通过用四原子连接基取代自然寡聚体中发现的正常磷酸二酯间糖链，形成独特的二核苷酸和多核苷酸，可用于调节RNA表达和治疗。还公开了合成和使用的方法。
• Two-Stage Synthesis of 3′-<i>O</i>-Tritylthymidine via Hydrolysis of 3′, 5′-Di-<i>O</i>-tritylthymidine; Comparison with Alternative Methods
  作者：L. C. Davies、P. B. Farmer、M. Jarman、J. A. Stock

  DOI：10.1055/s-1980-28965

  日期：——