cyanoethyl 5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl N-diisopropylphosphoramidate | 108678-08-6

• 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: cyanoethyl 5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl N-diisopropylphosphoramidate
• 英文别名: 5'-O-(4,4-dimethoxytrityl)-3′-[O-(2-cyanoethyl)phosphoramidyl(diisopropylamino)]deoxythymidine；dT-phosphoramidite；3-[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-[di(propan-2-yl)amino]phosphoryl]oxypropanenitrile
• CAS: 108678-08-6
• 化学式: C₄₀H₄₉N₄O₉P
• 分子量: 760.824
• InChiKey: VJOCUXODPFONTB-JYQXRUAGSA-N

物化性质

• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  54
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  149
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  cyanoethyl 5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl N-diisopropylphosphoramidate 以 N-甲基吡咯烷酮 、 乙腈 为溶剂， 反应 0.08h， 生成
  参考文献：
  名称：

  A new approach for pyrophosphate bond formation starting from phosphoramidite derivatives by use of 6-trifluoromethyl-1-hydroxybenzotriazole-mediated O–N phosphoryl migration

  摘要：

  A new method for pyrophosphate bond formation in the solid phase was developed by use of phosphoramidite derivatives, which were found to be readily converted by reaction with 6-trifluoroinethyl-1-hydroxybenztriazole via an O-N phosphoryl rearrangement into pentavalent phosphotriester intermediates. These intermediates proved to react smoothly with not only phomonoesters but also phosphodiesters to give protected pyrophosphate derivatives which, in turn, could be easily deprotected to give the desired pyrophosphate derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.11.110
• 作为产物：
  描述：

  5’-(4,4’-二甲氧基三苯基)-3’-脱氧胸苷 2’-(2-氰乙基-N,N-二异丙基)亚磷酰胺 在 叔丁基过氧化氢 作用下， 以 癸烷 、 乙腈 为溶剂， 反应 0.17h， 以80%的产率得到cyanoethyl 5'-O-(4,4'-dimethoxytrityl)thymidine-3'-yl N-diisopropylphosphoramidate
  参考文献：
  名称：

  无碱基保护，封端反应和PN键裂解反应的寡聚脱氧核苷酸合成的质子阻断策略。

  摘要：

  基于迄今为止最简单和合理的酸碱反应原理，开发了一种新的N-未保护的亚磷酰胺方法，称为“质子嵌段”方法，用于寡聚脱氧核苷酸的化学合成。该概念涉及用“质子”保护脱氧胞苷和脱氧腺苷的核碱基，以在缩合过程中通过使用pK（a）值低于2.8的启动子将它们转化为未反应的质子化碱基。将此策略应用于d [CpT]和d [ApT]的合成，以检查与碱基残基相关的副反应。在这种“质子阻断”方法中，发现三氟甲磺酸5-硝基苯并咪唑鎓（NBT）是最好的促进剂，THF优于CH（3）CN作为溶剂，因此可以大大抑制由于促进剂固有的酸性而引起的伴随的三苯甲基化反应。将该策略应用于固相合成，在HPLC分析中得到的d [CpT]，d [ApT]，d [ApA]，d [CpC]和d [GpT]几乎都是单峰。同样，成功合成了d [ApApApT]和d [CpCpCpT]，而没有明显的副反应。最后，以d [CpCpCpCpCpCpCpT]和d

  DOI：

  10.1021/jo034204k

文献信息

• 一种亚磷酰化试剂及其在寡核苷酸合成中的应用
  申请人：广州同隽医药科技有限公司

  公开号：CN111039977B

  公开（公告）日：2022-11-08

  本发明提供一种亚磷酰化试剂将其应用，该亚磷酰化试剂为2‑腈基乙氧基上有大非极性取代基团的2‑腈基乙氧基亚磷酰胺类化合物，该亚磷酰化试剂能与核苷单体或核苷酸片段3′‑OH或5′‑OH反应生成亚磷酰二酯，亚磷酰二酯在合适的活化剂作用下与另一组核苷单体或核苷酸片段3′‑OH或5′‑OH继续反应生成亚磷酰三酯，经过氧化或硫化得到磷酸三酯或硫代磷酸三酯，去保护得到寡核苷酸，整个过程中所有亚磷酸酯中间体或磷酸酯中间体易溶于中低极性的溶剂，在高极性溶剂中溶解度却很低，而其它的反应原料或副产物却易溶于高极性溶剂，因而能通过非极性/极性溶剂萃取进行纯化，使得后续的链增长反应不受阻碍，既适用于逐个核苷酸接入也适用于片段法接入的反应。
• Liquid-Phase RNA Synthesis by Using Alkyl-Chain-Soluble Support
  作者：Shokaku Kim、Masanori Matsumoto、Kazuhiro Chiba

  DOI：10.1002/chem.201300655

  日期：2013.6.24

  AbstractRecent progress in the RNA therapeutics has increased demand for the synthesis of large quantities of oligoribonucleotides. The assembly of RNA oligomers relies mainly on solid‐phase approaches. These allow rapid product purification and the ability to drive a target reaction to completion through the use of excess reagents. Despite the known advantages of solid‐phase synthesis, some issues in the process remain to be addressed, such as low and limited scale, reagent accessibility, and the use of a very large excess of reagents. Herein, we report a highly efficient and practical method of liquid‐phase synthesis of RNA oligomers by using alkyl‐chain‐soluble support. We demonstrate the utility of the liquid‐phase method through 21‐mer RNA synthesis on a gram scale.
• A NEW METHOD FOR OLIGONUCLEOTIDE DERIVATIZATION OF THE 3′ OR 5′- TERMINI WITH A CPG-SUPPORT CARRYING THE NATURAL PRODUCT ISOARGENTATIN-D
  作者：Paul Gaytán、Jorge Yañez、Xavier Soberón、Roberto Martínez

  DOI：10.1016/s0040-4039(97)01388-9

  日期：1997.9

  Oligonucleotides were modified at their 5' or 3'-termini using a CPG-support carrying isoargentatin-D, taking advantage of suitable commercial phosphoramidites to perform automated oligonucleotide synthesis in the 3'-->5' or 5'-->3' direction. (C) 1997 Elsevier Science Ltd.
• Method of Preparing Oligonucleotide Compounds
  申请人：Nogra Pharma Limited

  公开号：US20200392491A1

  公开（公告）日：2020-12-17

  The present invention relates to compositions comprising oligonucleotides, specifically SMAD7 antisense oligonucleotides, and methods for preparing the same.