(RS)-1-(7-methoxy-2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (RS)-1-(7-methoxy-2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil
• 英文别名: 5-fluoro-1-(7-methoxy-3,5-dihydro-2H-1,4-benzodioxepin-3-yl)pyrimidine-2,4-dione
• 化学式: C₁₄H₁₃FN₂O₅
• 分子量: 308.266
• InChiKey: JRMZVALEVUXDTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-羟基-5-甲氧基苄醇 在 三甲基氯硅烷 、 三氟化硼乙醚 、 四氯化锡 、 sodium hydride 、 potassium carbonate 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 181.0h， 生成 (RS)-1-(7-methoxy-2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil
  参考文献：
  名称：

  取代基对2-羟基苄醇衍生物与MEM氯化物反应模式的影响：七元和十元苯并稠合的O，O-缩醛的合成及机理方面

  摘要：

  （RS）-2-或（RS）-3-甲氧基-2,3-二氢-5 H -1,4-苯并二恶英和（RS）-5-或（RS）-3-甲氧基-2的合成，已经开发了3,5,6-四氢-8 H-苯并-[1,4,7]-三恶英。已经提出了通过三氟化硼醚化物促进的2-（甲氧基乙氧基甲氧基）苄氧基乙醛二甲基乙缩醛或2-（甲氧基乙氧基甲氧基甲基）苯氧基乙醛二甲基乙缩醛的转化的反应机理。该反应的跨环形式导致12元中间体容易缩合为10元和7元苯稠合的O，O-缩醛。副产物的表征强烈支持提出的机制。

  DOI：

  10.1016/j.tet.2004.09.077

文献信息

• Neighbouring-group participation as the key step in the reactivity of acyclic and cyclic salicyl-derived O,O-acetals with 5-fluorouracil. Antiproliferative activity, cell cycle dysregulation and apoptotic induction of new O,N-acetals against breast cancer cells
  作者：Estrella Saniger、Joaquı́n M Campos、Antonio Entrena、Juan A Marchal、Houria Boulaiz、Antonia Aránega、Miguel Á Gallo、Antonio Espinosa

  DOI：10.1016/j.tet.2003.08.016

  日期：2003.9

  The reaction between o-(hydroxymethyl)phenoxyacetaldehyde dimethyl acetals, or 3-methoxy-2,3-dihydro-5H-1,4-benzodioxepins with 5-fluorouracil (5-FU), has been studied. The intramolecular cyclization may be explained through a neighboring group attack to give a 2-(5-fluorouracil-1-yl)oxyranium ion that can be attacked by the silylated benzylic hydroxy group to yield the benzannelated seven-membered

  研究了邻-（羟甲基）苯氧基乙醛二甲基乙缩醛或3-甲氧基-2,3-二氢-5 H -1,4-苯并二恶英与5-氟尿嘧啶（5-FU）的反应。分子内环化可以通过相邻基团的进攻得到2-（5-氟尿嘧啶-1-基）氧基铀离子来解释，该离子可以被甲硅烷基化的苄基羟基进攻以产生苯甲酰化的七元O，N-乙缩醛。还报道了大环反式-双（5-FU O，N-缩醛）的形成。这种化合物将人MCF-7乳腺癌细胞阻滞在G o / G 1处细胞周期的阶段。相反，无环硝基O，N-缩醛似乎起5-FU前药的作用，因为它像众所周知的前药Ftorafur一样，将癌细胞阻滞在S期。
• Medium benzene-fused oxacycles with the 5-fluorouracil moiety: synthesis, antiproliferative activities and apoptosis induction in breast cancer cells
  作者：Estrella Saniger、Joaquı́n M Campos、Antonio Entrena、Juan A Marchal、Inés Suárez、Antonia Aránega、Duane Choquesillo、Juán Niclós、Miguel Á Gallo、Antonio Espinosa

  DOI：10.1016/s0040-4020(03)00871-8

  日期：2003.7

  On the basis of the increase in lipophilicity, novel benzannelated six- and seven-membered derivatives have been synthesized, starting from 2-hydroxybenzyl alcohols, 2-hydroxybenzaldehydes, and catechol. The X-ray structure of (RS)-1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil (5) is presented and compared with its conformational analysis at the semiempirical (AM1) and ab initio (6-31G*) levels and NOE effects. A good agreement between both experimental and theoretical data was found showing a chair conformation for the 2,3-dihydro-5H-1,4-dioxepin ring and an axial orientation of the 5-FU moiety on the C3 position. Compounds 5 and (RS)-1-(7methoxy-2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-5-fluorouracil (6) were found to be the most potent inhibitor of MCF-7 cells growth. (RS)1-(2,3-Dihydrobenzoxepin-2-yl)-5-fluorouracil (8) induced apoptosis up to 57.33% of cell population after 24 It. (C) 2003 Elsevier Science Ltd. All fights reserved.
• Substituent effects on the reaction mode between 2-hydroxybenzyl alcohol derivatives and MEM chloride: synthesis and mechanistic aspects of seven- and ten-membered benzo-fused O,O-acetals
  作者：Estrella Saniger、Mónica Díaz-Gavilán、Beatriz Delgado、Duane Choquesillo、Josefa M. González-Pérez、Stefania Aiello、Miguel Á. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1016/j.tet.2004.09.077

  日期：2004.12

  of (RS)-2- or (RS)-3-methoxy-2,3-dihydro-5H-1,4-benzodioxepins and (RS)-5- or (RS)-3-methoxy-2,3,5,6-tetrahydro-8H-benzo-[1,4,7]-trioxecins has been developed. The mechanism of such a reaction via the boron trifluoride etherate-promoted transformation of 2-(methoxyethoxymethoxy)benzyloxyacetaldehyde dimethyl acetals or 2-(methoxyethoxymethoxymethyl)phenyloxyacetaldehyde dimethyl acetals has been proposed

  （RS）-2-或（RS）-3-甲氧基-2,3-二氢-5 H -1,4-苯并二恶英和（RS）-5-或（RS）-3-甲氧基-2的合成，已经开发了3,5,6-四氢-8 H-苯并-[1,4,7]-三恶英。已经提出了通过三氟化硼醚化物促进的2-（甲氧基乙氧基甲氧基）苄氧基乙醛二甲基乙缩醛或2-（甲氧基乙氧基甲氧基甲基）苯氧基乙醛二甲基乙缩醛的转化的反应机理。该反应的跨环形式导致12元中间体容易缩合为10元和7元苯稠合的O，O-缩醛。副产物的表征强烈支持提出的机制。