N-1-(4'-seleno-β-D-ribofuranosyl)-uracil | 1006032-35-4

• 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: N-1-(4'-seleno-β-D-ribofuranosyl)-uracil
• 英文别名: 1-(4-seleno-β-D-ribofuranosyl)uracil；(-)-1-(4-seleno-D-ribofuranosyl)uracil；4'-selenouridine；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)selenolan-2-yl]pyrimidine-2,4-dione
• CAS: 1006032-35-4
• 化学式: C₉H₁₂N₂O₅Se
• 分子量: 307.165
• InChiKey: KTMSUQFNHACYJW-XVFCMESISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.74
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-1-(4'-seleno-β-D-ribofuranosyl)-uracil 在 吡啶 、 4-二甲氨基吡啶 、 4-甲基苯磺酸吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 40.75h， 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：

  2,3-O-异亚丙基-D-核糖酸 gamma-内酯 在 4-二甲氨基吡啶 、 selenium 、 sodium tetrahydroborate 、 三氟甲磺酸三甲基硅酯 、 水 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 72.58h， 生成 N-1-(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。
• Discovery of a New Template for Anticancer Agents: 2′-deoxy-2′-fluoro-4′-selenoarabinofuranosyl-cytosine (2′-F-4′-Seleno-ara-C)
  作者：Lak Shin Jeong、Dilip K. Tosh、Won Jun Choi、Sang Kook Lee、You-Jin Kang、Sun Choi、Jin Hee Lee、Hankil Lee、Hyuk Woo Lee、Hea Ok Kim

  DOI：10.1021/jm900852b

  日期：2009.9.10

  The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).
• Stereoselective Synthesis and Conformational Study of Novel 2′,3′-Didehydro-2′,3′-dideoxy-4′-selenonucleosides
  作者：Dilip K. Tosh、Won Jun Choi、Hea Ok Kim、Yoonji Lee、Shantanu Pal、Xiyan Hou、Jungwon Choi、Sun Choi、Lak Shin Jeong

  DOI：10.1021/jo8003277

  日期：2008.6.1

  Stereoselective synthesis of novel 2',3'-didehydro-2',3'dideoxy-4'-selenonnucleosides (4'-seleno-d4Ns) 4a-c was accomplished via 4'-selenoribofuranosyl pyrimidines 11a-c, as key intermediates. 4'-Selenoribofuranosyl pyrimidines 11a-c were efficiently synthesized from D-ribose or D-gulonic gamma-lactone using a Pummerer-type condensation as a key step. Introduction of 2',3'-double bond was achieved by treating cyclic 2',3'-thiocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine.
• Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction
  作者：Kumarasamy Jayakanthan、Blair D. Johnston、B. Mario Pinto

  DOI：10.1016/j.carres.2008.02.014

  日期：2008.7

  The syntheses of four selenonucleosides, namely 4 '-O-selenoadenosine, -cytidine, -thymidine, and -uridine are described. Commercially available D-ribonolactone was converted to the key intermediate 1,4-anhydro-4-seleno-D-ribitol in seven steps in overall excellent yield. Oxidation of the seleno-D-ribitol with MCPBA gave a single diastereomeric selenoxide in excellent yield, which upon Pummerer reaction in the presence of silylated purine or pyrimidine bases gave stereoselectively the corresponding 4'-beta-selenonucleosides. The stereochemistry at the anomeric center was determined by means of 1D-NOE experiments. (C) 2008 Elsevier Ltd. All rights reserved.
• First Synthesis of 4‘-Selenonucleosides Showing Unusual Southern Conformation
  作者：Lak Shin Jeong、Dilip K. Tosh、Hea Ok Kim、Ting Wang、Xiyan Hou、Ho Seop Yun、Youngjoo Kwon、Sang Kook Lee、Jungwon Choi、Long Xuan Zhao

  DOI：10.1021/ol7025558

  日期：2008.1.1

  The first synthesis of 4'-selenonucleosides was achieved using a Pummerer-type condensation as a key step. All stereoelectronic effects shown in 4'-oxonucleosides were overwhelmed by the size of selenium and steric interactions, driving the conformation to the C2'-endol C3'-exo twist (Southern) conformation.