乙基[(2R,3S,5R)-3-羟基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基[(2R,3S,5R)-2-(羟基甲基)-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-3-基]磷酸酯 | 35002-96-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 中文名称: 乙基[(2R,3S,5R)-3-羟基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基[(2R,3S,5R)-2-(羟基甲基)-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-3-基]磷酸酯
• 英文名称: thymidine 3'-[thymidine 5'-(ethyl phosphate)]
• 英文别名: TpEtT；Thymidylyl-(3'-5')-thymidin-ethylester；P-ethyl-thymidylyl-(3'->5')-thymidine；Dtpdt ethylphosphotriester；ethyl [(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] phosphate
• CAS: 35002-96-1
• 化学式: C₂₂H₃₁N₄O₁₂P
• 分子量: 574.481
• InChiKey: ZKKPILTYCWGWSA-KJOYEBRGSA-N

物化性质

• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  203
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  乙基[(2R,3S,5R)-3-羟基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基[(2R,3S,5R)-2-(羟基甲基)-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-3-基]磷酸酯 在 氨 作用下， 以 水 为溶剂， 反应 8.0h， 以45%的产率得到胸苷酰(3'->5')胸苷铵盐
  参考文献：
  名称：

  Synthesis of novel cationic spermine-conjugated phosphotriester oligonucleotide for improvement of cell membrane permeability

  摘要：

  A spermine-conjugated ethyl phosphotriester oligonucleotide was obtained by solid-phase synthesis based on phosphoramidite chemistry. The ethyl phosphotriester linkage was robust to exonuclease digestion and stable in fetal bovine serum. Cell membrane permeability of the spermine-conjugated ethyl phosphotriester oligonucleotide was studied by fluorescence experiments. The effective cell penetrating potency of the spermine-conjugated ethyl phosphotriester oligonucleotide was determined by confocal laser scanning microscopy and measurement of intracellular fluorescence intensity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.071
• 作为产物：
  描述：

  (2R,3S,5R)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl ethyl (((2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl) phosphate 在 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.17h， 生成 乙基[(2R,3S,5R)-3-羟基-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-2-基]甲基[(2R,3S,5R)-2-(羟基甲基)-5-(5-甲基-2,4-二氧代嘧啶-1-基)四氢呋喃-3-基]磷酸酯
  参考文献：
  名称：

  Transformation of DinucleosideS-Aryl Phosphorothioates into the CorrespondingO-Alkyl Phosphates by Use of Tributyltin Alkoxides

  摘要：

  通过使用S-芳基二核苷硫代磷酸酯与三丁基锡醇盐的反应，可以容易地获得几种烷基二核苷磷酸三酯。该反应在室温中性条件下进行。

  DOI：

  10.1246/cl.1992.1501

文献信息

• Asseline, U.; Barbier, C.; Thuong, N. T., Phosphorus and Sulfur and the Related Elements, 1986, vol. 26, p. 63 - 74
  作者：Asseline, U.、Barbier, C.、Thuong, N. T.

  DOI：——

  日期：——
• Transalkylation of Phosphotriesters Using Cob(I)alamin:  Toward Specific Determination of DNA−Phosphate Adducts
  作者：Johanna Haglund、Adnan Rafiq、Lars Ehrenberg、Bernard T. Golding、Margareta Törnqvist

  DOI：10.1021/tx990135m

  日期：2000.4.1

  The supernucleophilic cobalt compound, cob(I)alamin, has been kinetically characterized with respect to its ability to bring about transalkylation of adducts to DNA phosphates (phosphotriesters). The reactivity of cob(I)alamin toward different phosphotriesters (model compounds and methylated DNA), as well as its specificity toward DNA-phosphate adducts, has been investigated. Through nucleophilic displacement on the alkyl by cob(I)alamin, the alkyl groups (methyl and ethyl) were transferred from phosphotriesters within minutes at room temperature. In contrast, methylated nucleosides (base adducts) were stable in the presence of cob(I)alamin.
• UZNANSKI, BOGDAN;WILK, ANDRZEJ;STEC, WOJCIECH J., TETRAHEDRON. LETT., 28,(1987) N 29, 3401-3404
  作者：UZNANSKI, BOGDAN、WILK, ANDRZEJ、STEC, WOJCIECH J.

  DOI：——

  日期：——
• Synthesis of novel cationic spermine-conjugated phosphotriester oligonucleotide for improvement of cell membrane permeability
  作者：Junsuke Hayashi、Tomoko Hamada、Ikumi Sasaki、Osamu Nakagawa、Shun-ichi Wada、Hidehito Urata

  DOI：10.1016/j.bmcl.2015.06.071

  日期：2015.9

  A spermine-conjugated ethyl phosphotriester oligonucleotide was obtained by solid-phase synthesis based on phosphoramidite chemistry. The ethyl phosphotriester linkage was robust to exonuclease digestion and stable in fetal bovine serum. Cell membrane permeability of the spermine-conjugated ethyl phosphotriester oligonucleotide was studied by fluorescence experiments. The effective cell penetrating potency of the spermine-conjugated ethyl phosphotriester oligonucleotide was determined by confocal laser scanning microscopy and measurement of intracellular fluorescence intensity. (C) 2015 Elsevier Ltd. All rights reserved.
• Transformation of Dinucleoside<i>S</i>-Aryl Phosphorothioates into the Corresponding<i>O</i>-Alkyl Phosphates by Use of Tributyltin Alkoxides
  作者：Shokichi Ohuchi、Hiroshi Ayukawa、Tsujiaki Hata

  DOI：10.1246/cl.1992.1501

  日期：1992.8

  Several alkyl dinucleoside phosphotriesters were easily obtained by use of the reaction of S-aryl dinucleoside phosphorothioates with tributyltin alkoxides. This reaction proceeds at room temperature under neutral conditions.

  通过使用S-芳基二核苷硫代磷酸酯与三丁基锡醇盐的反应，可以容易地获得几种烷基二核苷磷酸三酯。该反应在室温中性条件下进行。