5’-O-4,4'-dimethoxytrityl-5-fluorouridine | 157770-09-7

• 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: 5’-O-4,4'-dimethoxytrityl-5-fluorouridine
• 英文别名: 5'-O-(4,4'-dimethoxytrityl)-5-fluorouridine；5'-O-[4,4'-dimethoxytrityl]-5-fluorouridine；1-[(2R,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3,4-dihydroxyoxolan-2-yl]-5-fluoropyrimidine-2,4-dione
• CAS: 157770-09-7
• 化学式: C₃₀H₂₉FN₂O₈
• 分子量: 564.567
• InChiKey: NGOGXTKTRUWNEZ-IYUNARRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5’-O-4,4'-dimethoxytrityl-5-fluorouridine 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 5'-O-(4,4'-dimethoxytrityl)-2'-O-(tert-butyldimethylsilyl)-5-fluorouridine 3'-(cyanoethyl N,N-diisopropylphosphoramidite)
  参考文献：
  名称：

  Synthesis of 5'-O-(4,4'-Dimethoxytrityl)-2'-O-(tert-butyldimethylsilyl)-5-fluorouridine 3'-(Cyanoethyl N,N-diisopropylphosphoramidite) and Its Use in the Synthesis of RNA

  摘要：

  5-Fluorouridine (FUrd) has been successfully converted to 5'-O-(4,4'-dimethoxytrityl)-2'-O-(tert-butyldimethylsilyl)-5-fluorouridine 3'-(cyanoethyl N,N-diisopropyl(phosphoramidite) by methods similar to those employed for the preparation of other ribonucleoside phosphoramidites. The desired product, as well as its precursors and the incorrect regioisomers, are prepared and fully characterized by H-1 NMR, F-19 NMR, P-31 NMR, FAR-MS, UV absorbance, elemental analysis, and melting points. The purified material is used for the production of RNA by solid-phase methods. Coupling yields of 94% are obtained with this material. The resulting RNA is readily purified and used for biophysical studies. The self-complemetary RNA decamer 5'-rGCGAAU(FU)CGC is prepared and purified. The material adopts an A-form duplex in solution at neutral pH as characterized by CD spectroscopy. The thermal stability of the duplex is similar to the parent duplex oligoribonucleotide prepared with uridine instead of 5-fluorouridine. The control duplex has a T-m of 53.8 and the FUrd substituted duplex has a T-m of 56.6 (xb0)degrees C as determined by UV hyperchromicity at 260 nm. The CD spectra and UV hyperchromicity data for the duplex oligoribonucleotide containing FUrd have a slight pH dependence indicating that ionization of FUrd has a slight but measurable impact on RNA duplex stability. 1D NMR spectroscopy of the imino hydrogens for this duplex in H2O solution confirms the formation of Watson-Crick base pairs. The imino hydrogen resonance for the FUrd-A base pair is moved downfield and broadened compared with a control duplex oligoribonucleotide as a consequence of the electron-withdrawing inductive effect of fluorine.

  DOI：

  10.1021/jo00098a044
• 作为产物：
  描述：

  4,4'-双甲氧基三苯甲基氯 以 吡啶 、 二氯甲烷 、 氯仿 、 5-氟尿嘧啶核苷 为溶剂， 生成 5’-O-4,4'-dimethoxytrityl-5-fluorouridine
  参考文献：
  名称：

  Oligonucleotides containing 5-fluorouracil

  摘要：

  一种由5-氟尿嘧啶5'-单磷酸或5-氟脱氧尿嘧啶5'-单磷酸构成的2至26个单体的同源寡核苷酸，通过3'-到5'-磷酸二酯键共价连接，其中在3'-或5'-端上共价连接了来自胆固醇、乙基间隔的金刚烷、1,2-二十六烷基甘油或聚-L-赖氨酸的分子。这些同源寡核苷酸表现出抗肿瘤活性。

  公开号：

  US05457187A1

文献信息

• Anti-flavivirus Activity of Different Tritylated Pyrimidine and Purine Nucleoside Analogues
  作者：Christopher McGuigan、Michaela Serpi、Magdalena Slusarczyk、Valentina Ferrari、Fabrizio Pertusati、Silvia Meneghesso、Marco Derudas、Laura Farleigh、Paola Zanetta、Joachim Bugert

  DOI：10.1002/open.201500216

  日期：2016.6

  A series of tritylated and dimethoxytritylated analogues of selected pyrimidine and purine nucleosides were synthesized and evaluated for their in vitro inhibitory activity against two important members of the genus Flavivirus in the Flaviviridae family, the yellow fever (YFV) and dengue viruses (DENV). Among all compounds tested, the 5′‐O‐tritylated and the 5′‐O‐dimethoxytritylated 5‐fluorouridine

  合成了一系列选定的嘧啶和嘌呤核苷的三苯甲基化和二甲氧基三苯甲基化的类似物，并评估了它们对黄病毒科中黄病毒属的两个重要成员黄热病和登革热病毒的体外抑制活性。在所有测试的化合物中，5'-O-三苯甲基化和5'-O-二甲氧基三苯甲基化的5-氟尿苷衍生物均具有抗YFV的能力。有趣的是，在嘌呤类似物系列中，5'O，N-双三苯甲基化的氟达拉滨衍生物在μm浓度下表现出对DENV的强抑制活性，但对YFV的效力却明显减弱。
• 5-Fluoro-4-thiouridine phosphoramidite: New synthon for introducing photoaffinity label into oligodeoxynucleotides
  作者：Jan Milecki、Joanna Nowak、Bohdan Skalski、Stefan Franzen

  DOI：10.1016/j.bmc.2011.08.035

  日期：2011.10

  appropriate set of protecting groups was optimized including the 4-thio function introduced via 4-triazolyl as the 4-(2-cyanoethyl)thio derivative, and the t-butyldimethyl silyl for 2′ and 3′ hydroxyl protection, enabling efficient synthesis of the phosphoramidite. These protecting groups prevented unwanted side reactions during oligonucleotide synthesis. The utility of the proposed synthetic route was proven

  描述了5-氟-4-硫代2'- O-甲基尿苷的亚磷酰胺的合成。优化了一组合适的保护基团，包括通过4-三唑基作为4-（2-氰基乙基）硫代衍生物引入的4-硫基官能团，以及用于2'和3'羟基保护的叔丁基二甲基甲硅烷基，从而能够有效地合成亚磷酰胺。这些保护基团防止了寡核苷酸合成过程中的有害副反应。通过自动合成制备几种寡核苷酸，证明了所提出的合成路线的实用性。光化学实验证实了合成子的实用性。
• US5457187A
  申请人：——

  公开号：US5457187A

  公开（公告）日：1995-10-10
• US5614505A
  申请人：——

  公开号：US5614505A

  公开（公告）日：1997-03-25
• US5663321A
  申请人：——

  公开号：US5663321A

  公开（公告）日：1997-09-02