4-ethoxy-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone | 59495-20-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 4-ethoxy-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone
• 英文别名: 4-O-ethyluridine；4-ethoxy-1-β-D-ribofuranosyl-2(1H)-pyrimidone；4-ethoxy-1-(β-D-ribofuranosyl)pyrimidine；O⁴-Ethyluridin；4-ethoxy-1-β-D-ribofuranosyl-1H-pyrimidin-2-one；O⁴-ethyl-uridine；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-ethoxypyrimidin-2-one
• CAS: 59495-20-4
• 化学式: C₁₁H₁₆N₂O₆
• 分子量: 272.258
• InChiKey: XMDCFRVNLHCIPD-PEBGCTIMSA-N

物化性质

• 沸点：
  490.3±55.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-ethoxy-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone 在 2,6-二甲基吡啶 、 重铬酸吡啶 、 samarium diiodide 、 zinc dibromide 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 为溶剂， 反应 62.16h， 生成 1-[(2R,3R,3aR,7aR)-3-[tert-butyl(dimethyl)silyl]oxy-3a-hydroxy-5-oxo-3,4,7,7a-tetrahydro-2H-furo[2,3-c]pyran-2-yl]-4-ethoxypyrimidin-2-one
  参考文献：
  名称：

  Nucleosides and Nucleotides. 163. Synthesis of 3‘-β-Branched Uridine Derivatives via Intramolecular Reformatsky-Type Reaction Promoted by Samarium Diiodide¹

  摘要：

  A novel efficient method for the synthesis of 3'-beta-branched uridines starting from uridine was developed, in which a SmI2-promoted intramolecular Reformatsky-type reaction was effectively used. 5'-O-(Bromoacetyl)-3'-ketouridine derivatives 12, 26, and 27 were synthesized from uridine and were subjected to an intramolecular Reformatsky-type reaction. When 12, 26, and 27 were treated with 2.0 equiv of SmI2 in THF at -78 degrees C, intramolecular carbon-carbon bond formation at the 3'-beta-position proceeded smoothly to give the corresponding 3',5'-lactones 14, 28, and 29 in high yields, respectively. Treatment of 28 with NH3/MeOH gave the 3'-beta-branched uridine derivative 32 quantitatively, which was then deprotected to give 3'-C-(carbamoylmethyl)uridine (33).

  DOI：

  10.1021/jo961665f
• 作为产物：
  描述：

  2',3',5'-三乙酰尿苷 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 9.5h， 生成 4-ethoxy-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone
  参考文献：
  名称：

  嘧啶2'-酮核苷的烷基加成反应：2'-支链糖嘧啶核苷的合成（核苷和核苷酸.LXXXI。

  摘要：

  4-乙氧基-1-(3,5-O-四异丙基二硅氧烷-1,3-二基-β-D-赤式-戊呋喃-2-糖基)-2(1H)-嘧啶酮(11)与各种有机金属试剂反应，生成了相应的2'-支链糖嘧啶核苷。只有在与MeMgBr和EtMgBr的反应中，观察到更受阻的β-进攻，得到了2'-烷基呋喃糖苷(13a, b)。在11与MeLi、Me3Al或PhMgBr的反应中，立体选择性地得到了2'-甲基或苯基阿拉伯糖苷(12a, b, c)。还描述了这些嘧啶核苷转化为胞嘧啶衍生物的过程，并讨论了它们的抗白血病和抗病毒活性。

  DOI：

  10.1248/cpb.36.945

文献信息

• Treatment of carcinoma by administration of
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05607925A1

  公开（公告）日：1997-03-04

  This invention relates to certain novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease states.

  这项发明涉及某些新型的2'-卤代甲基亚甲基、2'-乙烯基亚甲基和2'-乙炔基胞嘧啶、尿苷和鸟苷衍生物及其组合物，这些衍生物在治疗罹患肿瘤或病毒性疾病状态的患者中具有用途。
• 2-'-ethenylidene cytidine, uridine and guanosine derivatives
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05616702A1

  公开（公告）日：1997-04-01

  This invention relates to certain novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease states.

  这项发明涉及某些新颖的2'-卤代甲基亚甲基、2'-乙烯基亚甲基和2'-乙炔基胞苷、尿苷和鸟苷衍生物，以及这些衍生物的组合物，这些衍生物在治疗患有肿瘤性或病毒性疾病状态的患者中是有用的。
• 2'-halomethylidene cytidine, uridine and guanosine compounds and their
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05378693A1

  公开（公告）日：1995-01-03

  This invention relates to certain novel 2'-halomethylidene, 2'-ethenylidene and 2'-ethynyl cytidine, uridine and guanosine derivatives, and compositions thereof, which are useful in the treatment of patients afflicted with neoplastic or viral disease states.

  这项发明涉及某些新型的2'-卤代甲基亚甲基、2'-乙烯基亚甲基和2'-乙炔基胞苷、尿苷和鸟苷衍生物，以及这些衍生物的组合物，这些衍生物在治疗患有肿瘤或病毒性疾病状态的患者中非常有用。
• Molecular Design of a New Class of Spin-Labeled Ribonucleosides with <i>N</i>-<i>tert</i>-Butylaminoxyl Radicals
  作者：Mariko Aso、Takeshi Ikeno、Kouji Norihisa、Masakazu Tanaka、Noboru Koga、Hiroshi Suemune

  DOI：10.1021/jo015532s

  日期：2001.5.1

  corresponding stable spin-labeled nucleosides (8a-d and 1a-d), which were confirmed by EPR spectroscopy. Similarly, the precursors of spin-labeled pyrimidines (13, 20, and 23) were synthesized by site-selective lithiation of tri-O-protected pyrimidine derivatives (9, 18, and 21) followed by the reaction with MNP and deprotection. An EPR study showed that the aminoxyl radicals (2, 3, and 4) were stable and that

  我们设计了一种新的自旋标记核苷，其带有一个N-叔丁基氨基羟自由基，该自由基被直接引入到核碱基中。合成了含有氨基基团（例如1a-d，2、3和4）的嘌呤和嘧啶核糖核苷，以研究N-叔丁基氨基甲氧基在核碱基上的稳定性和行为。三-O-甲硅烷基化的6-氯嘌呤核糖核苷（5）的锂化，然后与2-甲基-2-亚硝基丙烷（MNP）反应，得到关键化合物6a，将其进一步转化为6b-d。用Ag（2）O氧化获得的6a-d及其三醇（7a-d）导致形成相应的稳定自旋标记核苷（8a-d和1a-d），这已通过EPR光谱法确认。同样，自旋标记的嘧啶的前体（13，20，通过将三-O-保护的嘧啶衍生物（9、18和21）进行位点选择性锂化，然后与MNP反应并进行脱保护，来合成α-α和β-α和β-α和β-α-α-β-α-β-α-α-β-氨基吗啉。EPR研究表明，氨氧自由基（2、3和4）是稳定的，它们的超精细结构取决于自由基的位置。嘧啶的电子密度也影响超精细结构。
• 2'-ALKYLIDENEPYRIMIDINE NUCLEOSIDE DERIVATIVES, PROCESS FOR THEIR PREPARATION, AND THEIR USE
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：EP0310673A1

  公开（公告）日：1989-04-12

  Novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula (I) or salts thereof are disclosed, wherein R1 represents an amino group or a hydroxy group, R2 represents a hydrogen atom, a halogen atom or a lower alkyl group, R3 represents a hydrogen atom or a lower alkyl group, and R4 represents a hydrogen atom or a phosphoric acid residue. These novel compounds may be prepared by using a uridine or cytidine derivative as the starting material and introducing an alkylidene group into the 2'-position of the sugar moiety with a Wittig reagent. These compounds have an excellent antiviral effect, thus providing novel antiviral drugs.

  由式(I)表示的新型 2'-烷基亚嘧啶核苷衍生物 或其盐，其中 R1 代表氨基或羟基，R2 代表氢原子、卤素原子或低级烷基，R3 代表氢原子或低级烷基，R4 代表氢原子或磷酸残基。这些新型化合物的制备方法是：以尿苷或胞苷衍生物为起始原料，用维蒂希试剂在糖分子的 2'- 位上引入亚烷基。这些化合物具有极佳的抗病毒效果，从而提供了新型抗病毒药物。