1-(2,2’-anhydro-4-seleno-β-D-ribofuranosyl)uracil | 1620879-55-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(2,2’-anhydro-4-seleno-β-D-ribofuranosyl)uracil
• 英文别名: (-)-2,2'-anhydro-1-(4-seleno-D-arabinofuranosyl)uracil
• CAS: 1620879-55-1
• 化学式: C₉H₁₀N₂O₄Se
• 分子量: 289.149
• InChiKey: SDOQZIMHDXDMHJ-CCXZUQQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.64
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  84.58
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-(2,2’-anhydro-4-seleno-β-D-ribofuranosyl)uracil 在 吡啶 、 4-二甲氨基吡啶 、 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 35.0h， 生成 2,2'-anhydro-1-(3-O-tetrahydropyranyl-5-O-trityl-4-seleno-D-arabinofuranosyl)uracil
  参考文献：
  名称：

  Structure–activity relationships of 2′-modified-4′-selenoarabinofuranosyl-pyrimidines as anticancer agents

  摘要：

  Based on the potent anticancer activity of the D-arabino-configured cytosine nucleoside ara-C, novel 2'-substituted-4'-selenoarabinofuranosyl pyrimidines 3a-3u, comprising azido, fluoro, and hydroxyl substituents at C-2' were designed, synthesized, and evaluated for anticancer activity. The 2'-azido group was stereoselectively introduced by the Mitsunobu reaction using diphenylphosphoryl azide (DPPA), and the 2'-fluoro group was stereoselectively introduced through the double inversions of stereochemistry via the episelenium intermediate, which was formed by the participation of the selenium atom. Among the compounds tested, the 2'-fluoro derivative 3t (X = NH2, Y = H, R = F) was found to be the most potent anticancer agent and showed more potent anticancer activity than the control, ara-C in all tested human cancer cell lines (HCT116, A549, SNU638, T47D, and PC-3) except the leukemia cell lines (K562). The anticancer activity of the 2'-substituted-4'-selenonucleosides is in the following order: 2'-F > 2'-OH > 2'-N3.

  DOI：

  10.1016/j.ejmech.2014.06.031
• 作为产物：
  描述：

  1-(5-O-tert-butyldiphenylsilyl-2,3-O-isopropylidene-4-seleno-β-D-ribofuranosyl)uracil 在 吡啶 、 4-二甲氨基吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 20.75h， 生成 1-(2,2’-anhydro-4-seleno-β-D-ribofuranosyl)uracil
  参考文献：
  名称：

  Structure–activity relationships of 2′-modified-4′-selenoarabinofuranosyl-pyrimidines as anticancer agents

  摘要：

  Based on the potent anticancer activity of the D-arabino-configured cytosine nucleoside ara-C, novel 2'-substituted-4'-selenoarabinofuranosyl pyrimidines 3a-3u, comprising azido, fluoro, and hydroxyl substituents at C-2' were designed, synthesized, and evaluated for anticancer activity. The 2'-azido group was stereoselectively introduced by the Mitsunobu reaction using diphenylphosphoryl azide (DPPA), and the 2'-fluoro group was stereoselectively introduced through the double inversions of stereochemistry via the episelenium intermediate, which was formed by the participation of the selenium atom. Among the compounds tested, the 2'-fluoro derivative 3t (X = NH2, Y = H, R = F) was found to be the most potent anticancer agent and showed more potent anticancer activity than the control, ara-C in all tested human cancer cell lines (HCT116, A549, SNU638, T47D, and PC-3) except the leukemia cell lines (K562). The anticancer activity of the 2'-substituted-4'-selenonucleosides is in the following order: 2'-F > 2'-OH > 2'-N3.

  DOI：

  10.1016/j.ejmech.2014.06.031

文献信息

• Synthesis and biological evaluation of 2′-substituted-4′-selenoribofuranosyl pyrimidines as antitumor agents
  作者：Varughese Alexander、Jayoung Song、Jinha Yu、Jung Hee Choi、Jin-Hee Kim、Sang Kook Lee、Won Jun Choi、Lak Shin Jeong

  DOI：10.1007/s12272-014-0466-6

  日期：2015.6

  The 2′-substituted-4′-selenoribofuranosyl pyrimidines 3a–3j were synthesized from D-ribose and assayed for anticancer activity. The 2′-azido and 2′-fluoro groups with a ribo configuration were introduced by the regioselective opening of the O2,2′-anhydronucleosides with sodium azide and (HF)x-pyridine, respectively. Among the compounds tested, only 2′-fluoro derivative 3j was found to exhibit significant anticancer activity, but was much less potent than the corresponding 2′-arabino analogue 2c. This study will provide medicinal chemists with the insight into the identification of structural requirements for the anticancer activity for the developments of biologically active nucleosides.

  由 D-核糖合成 2'-取代-4'-硒代核糖呋喃糖基嘧啶 3a-3j，并测定其抗癌活性。具有核糖构型的2'-叠氮基和2'-氟基团是通过分别用叠氮化钠和(HF)x-吡啶对O2,2'-脱水核苷进行区域选择性打开而引入的。在测试的化合物中，只有2'-氟衍生物3j被发现表现出显着的抗癌活性，但其效力远低于相应的2'-阿拉伯类似物2c。这项研究将为药物化学家提供深入了解抗癌活性的结构要求的鉴定，以开发生物活性核苷。
• First Synthesis of Fully Modified 4′-SelenoRNA and 2′-OMe-4′-selenoRNA Based on the Mechanistic Considerations of an Unexpected Strand Break
  作者：Noriko Tarashima、Koya Hayashi、Maki Terasaki、Hirotsugu Taniike、Yusuke Inagaki、Kenji Hirose、Kazuhiro Furukawa、Akira Matsuda、Noriaki Minakawa

  DOI：10.1021/ol502077h

  日期：2014.9.19

  This study investigated oligonucleotide (ON) synthesis containing 4'-selenoribonucleoside(s) under standard phosphoramidite conditions. Careful operation using a manual ON synthetic system revealed that an unexpected strand break occurred to afford a C2-symmetric homodimer as a byproduct. In addition, this side reaction occurred during I2 oxidation. On the basis of these findings, the first synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA was achieved using tert-butyl hydroperoxide (TBHP) as the alternative oxidant.