5'-O-(4,4'-dimethoxytrityl)-3'-O-levulinyl dithymidyl 2-cyanoethyl phosphate | 224186-67-8

• 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)-3'-O-levulinyl dithymidyl 2-cyanoethyl phosphate
• 英文别名: [(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-(2-cyanoethoxy)phosphanyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-oxopentanoate
• CAS: 224186-67-8
• 化学式: C₄₉H₅₄N₅O₁₅P
• 分子量: 983.966
• InChiKey: LMFSUJVTJMHMPK-WRRDGYDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  70
• 可旋转键数：
  23
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  240
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-3'-O-levulinyl dithymidyl 2-cyanoethyl phosphate 在 sulfur 作用下， 以 吡啶 为溶剂， 反应 0.5h， 生成 [(2R,3S,5R)-2-[[[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-(2-cyanoethoxy)phosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-oxopentanoate
  参考文献：
  名称：

  Investigation of a Facile Synthetic Method for Phosphorothioate Dimer Synthons In Oligonucleotide Phosphorothioates Synthesis

  摘要：

  A facile synthetic method of a phosphorothioate dimer block was investigated. Dinucleoside phosphite triester intermediates were obtained in one-pot synthesis by the coupling of a protected nucleoside bearing free 5'-OH and a protected nucleoside bearing free 3'-OH in the presence of phosphorous trichloride (PCl3) and 1,2,4-triazole. The intermediates were easily sulfurized to afford the desired phosphorothioate dimer blocks in 33-64% overall yields.

  DOI：

  10.1080/15257770008033035
• 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 、 3'-O-levulinoylthymidine 在 四氮唑 作用下， 以 乙腈 为溶剂， 反应 0.75h， 生成 5'-O-(4,4'-dimethoxytrityl)-3'-O-levulinyl dithymidyl 2-cyanoethyl phosphate
  参考文献：
  名称：

  SULFUR TRANSFER REAGENTS FOR OLIGONUCLEOTIDE SYNTHESIS

  摘要：

  本发明公开了N-甲酰基-5-氨基-3H-1,2,4-二噻唑-3-硫酮作为新型高效硫转移试剂的使用。通过31P NMR和HPLC研究了这些试剂向含有P（III）原子、三苯基膦、5'-O-DMT-胸腺嘧啶-2-氰基乙基（N,N-二异丙基）磷酰胺和5'-O-DMT-3'-O-左旋糖酰基二胸腺嘧啶基2-氰基乙基亚磷酸酯化合物中的硫转移。此外，还通过磷酰胺法研究了这些化合物在寡核苷酸磷酸硫酯的固相合成中的硫转移。在该应用中，2'-脱氧寡核苷酸的硫转移反应效率高达99.5%以上。这些新型硫化试剂可以使用简单的化学方法低成本合成。与许多已知的硫转移试剂（如1,2-苯并二噻唑-3-酮-1,1-二氧化物（Beaucage试剂）和5-乙氧基-3H-1,2,4-二噻唑-2-酮（EDIT））相比，本发明公开的硫化试剂在溶液中高度稳定，从而增加了它们的实用和商业价值。

  公开号：

  US20090306358A1

文献信息

• SULFUR TRANSFER REAGENTS FOR OLIGONUCLEOTIDE SYNTHESIS
  申请人：Guzaev Andrei P.

  公开号：US20090306358A1

  公开（公告）日：2009-12-10

  The use of N-formamidino-5-amino-3H-1,2,4-dithiazole-3-thiones as novel, efficient sulfur-transfer reagents is disclosed. The sulfur transfer from these reagents to compounds containing P(III) atom, triphenylphosphine, 5′-O-DMT-thymidine 2-cyanoethyl-(N,N-diisopropyl)phosphoramidite, and 5′-O-DMT-3′-O-levulinyl dithymidilyl 2-cyanoethyl phosphite, was studied in solution by 31 P NMR and HPLC. The sulfur transfer from title compounds was also studied in the solid-phase synthesis of oligonucleotide phosphorothioates by phosphoramidite methods. In this application, the efficiency of the sulfur transfer reaction for 2′-deoxyoligonucleotides was better than 99.5%. The novel sulfurizing agents are synthesized, at low cost, using simple chemical methods. As opposed to many sulfur transfer reagents known in the prior art such as 1,2-benzodithiol-3-one-1,1-dioxide (Beaucage reagent) and 5-ethoxy-3H-1,2,4-dithiazole-2-one (EDIT), the sulfurizing agents disclosed herein are highly stable in solution, which increases their practical and commercial value.

  本发明公开了N-甲酰基-5-氨基-3H-1,2,4-二噻唑-3-硫酮作为新型高效硫转移试剂的使用。通过31P NMR和HPLC研究了这些试剂向含有P（III）原子、三苯基膦、5'-O-DMT-胸腺嘧啶-2-氰基乙基（N,N-二异丙基）磷酰胺和5'-O-DMT-3'-O-左旋糖酰基二胸腺嘧啶基2-氰基乙基亚磷酸酯化合物中的硫转移。此外，还通过磷酰胺法研究了这些化合物在寡核苷酸磷酸硫酯的固相合成中的硫转移。在该应用中，2'-脱氧寡核苷酸的硫转移反应效率高达99.5%以上。这些新型硫化试剂可以使用简单的化学方法低成本合成。与许多已知的硫转移试剂（如1,2-苯并二噻唑-3-酮-1,1-二氧化物（Beaucage试剂）和5-乙氧基-3H-1,2,4-二噻唑-2-酮（EDIT））相比，本发明公开的硫化试剂在溶液中高度稳定，从而增加了它们的实用和商业价值。
• Investigation of a Facile Synthetic Method for Phosphorothioate Dimer Synthons In Oligonucleotide Phosphorothioates Synthesis
  作者：Takanori Miyashita、Kohei Yamada、Kazuhiko Kondo、Kenya Mori、Kazuo Shinozuka

  DOI：10.1080/15257770008033035

  日期：2000.5

  A facile synthetic method of a phosphorothioate dimer block was investigated. Dinucleoside phosphite triester intermediates were obtained in one-pot synthesis by the coupling of a protected nucleoside bearing free 5'-OH and a protected nucleoside bearing free 3'-OH in the presence of phosphorous trichloride (PCl3) and 1,2,4-triazole. The intermediates were easily sulfurized to afford the desired phosphorothioate dimer blocks in 33-64% overall yields.
• High-Yield Solution-Phase Synthesis of Di- and Trinucleotide Blocks Assisted by Polymer-Supported Reagents
  作者：Cécile Dueymes、Andreas Schönberger、Ilaria Adamo、Aude-Emmanuelle Navarro、Albert Meyer、Meinolf Lange、Jean-Louis Imbach、Fritz Link、François Morvan、Jean-Jacques Vasseur

  DOI：10.1021/ol0511777

  日期：2005.8.1

  [GRAPHICS]A new solution-phase phosphoramidite approach is reported for oligonucleotide synthesis employing recyclable solid-supported reagents. It uses polyvinyl pyridinium tosylate as the activator of a nucleoside-3'-O-phosphoramidite in the coupling step with a 5'-OH nucleoside or dinucleotide. The resulting phosphite triester was either sulfurized or oxidized using polystyrene-bound trimethylammonium tetrathionate or periodiate. This method avoids complicated purification steps, as excess reagents are easily removed by filtration.
• Improved Impurity Profile of Phosphorothioate Oligonucleotides Through the Use of Dimeric Phosphoramidite Synthons
  作者：Achim H. Krotz、Patrick Klopchin、Douglas L. Cole、Vasulinga T. Ravikumar

  DOI：10.1080/07328319708006244

  日期：1997.7

  Phosphorothioate oligonucleotides synthesized through assembly of dimeric phosphoramidite synthons show a significantly improved impurity profile compared to oligomers synthesized through coupling of standard monomer phosphoramidites. A greater than 70% reduction of the (n-1)-mer population and a ca. 50% reduction of phosphodiester linkages has been achieved.
• Reactivity of 3H-1,2,4-dithiazole-3-thiones and 3H-1,2-dithiole-3-thiones as sulfurizing agents for oligonucleotide synthesis
  作者：Andrei P. Guzaev

  DOI：10.1016/j.tetlet.2010.11.086

  日期：2011.1

  The reactivity of 5-amino-3H-1,2,4-dithiazole-3-thiones substituted at their amino group and 5-amino-3H-1,2-dithiole-3-thiones substituted at their amino group and C4 toward compounds containing P(III) atoms has been studied. N,N-Disubstituted-N'-(3-thioxo-3H-1,2,4-dithiazol-5-yl)methanimidamides were selected as novel efficient sulfur transfer reagents suitable for DNA and RNA synthesis. (C) 2010 Elsevier Ltd. All rights reserved.