(Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione

• 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: (Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-fluoro-1-[(2Z)-2-[5-oxo-3,4-bis(phenylmethoxy)furan-2-ylidene]ethyl]pyrimidine-2,4-dione
• 化学式: C₂₄H₁₉FN₂O₆
• 分子量: 450.423
• InChiKey: GOIBLDTYIQCWGA-ODLFYWEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione 在 氨 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 24.0h， 以36.17%的产率得到1-[2-(2-amino-3,4-bis-benzyloxy-5-oxo-2,5-dihydro-furan-2-yl)-ethyl]-5-fluoro-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  l-抗坏血酸的新的5或6-氮杂嘧啶和氰尿酸衍生物，在烯键间隔基上带有游离C -5羟基或C -4氨基：CD光谱绝对构型测定和生物活性评估

  摘要：

  我们对新颖类型胞嘧啶和5-氮杂胞嘧啶（的合成报告19），尿嘧啶和6-氮尿嘧啶（13 - 18和氰尿酸（）19 - 22）的衍生物升抗坏血酸，以及它们的抑制细胞生长的人体恶性肿瘤细胞系与肝癌细胞活性的评价。它们对人正常成纤维细胞（WI38）的细胞毒性作用。CD谱分析表明，胞嘧啶（5和6），尿嘧啶（14 - 16），6-氮尿嘧啶（17），氰尿酸（21）的衍生物升-在烯键间隔基上带有游离氨基的抗坏血酸以对映异构体的外消旋混合物的形式存在，而在烯键间隔基上含有C -5取代羟基的L-抗坏血酸衍生物以（4 R， 5 S）对映体形式获得。通过X射线晶体结构分析证实了1-抗坏血酸（13）的6-氮杂尿嘧啶衍生物的立体化学。这些分子通过一个N–H⋯O氢键，两个C–H⋯O氢键和两个C–H⋯π相互作用自组装成三维框架。细胞抑制活性评估表明化合物对测试的细胞系没有显示出明显的抗增殖作用。但是，l的胞嘧啶衍生物-含有C

  DOI：

  10.1016/j.ejmech.2011.03.066
• 作为产物：
  描述：

  5-氟脲嘧啶 、 5,6-di-O-acetyl-2,3-di-O-benzyl-L-ascorbic acid 在 硫酸氢铵 、 六甲基二硅氮烷 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 15.0h， 生成 (Z)-1-(2-(3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene)ethyl)-5-fluoropyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  l-抗坏血酸的新的5或6-氮杂嘧啶和氰尿酸衍生物，在烯键间隔基上带有游离C -5羟基或C -4氨基：CD光谱绝对构型测定和生物活性评估

  摘要：

  我们对新颖类型胞嘧啶和5-氮杂胞嘧啶（的合成报告19），尿嘧啶和6-氮尿嘧啶（13 - 18和氰尿酸（）19 - 22）的衍生物升抗坏血酸，以及它们的抑制细胞生长的人体恶性肿瘤细胞系与肝癌细胞活性的评价。它们对人正常成纤维细胞（WI38）的细胞毒性作用。CD谱分析表明，胞嘧啶（5和6），尿嘧啶（14 - 16），6-氮尿嘧啶（17），氰尿酸（21）的衍生物升-在烯键间隔基上带有游离氨基的抗坏血酸以对映异构体的外消旋混合物的形式存在，而在烯键间隔基上含有C -5取代羟基的L-抗坏血酸衍生物以（4 R， 5 S）对映体形式获得。通过X射线晶体结构分析证实了1-抗坏血酸（13）的6-氮杂尿嘧啶衍生物的立体化学。这些分子通过一个N–H⋯O氢键，两个C–H⋯O氢键和两个C–H⋯π相互作用自组装成三维框架。细胞抑制活性评估表明化合物对测试的细胞系没有显示出明显的抗增殖作用。但是，l的胞嘧啶衍生物-含有C

  DOI：

  10.1016/j.ejmech.2011.03.066

文献信息

• Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives of 2,3-<i>O</i>,<i>O</i>-Dibenzyl-6-deoxy-<scp>l</scp>-ascorbic Acid and 4,5-Didehydro-5,6- dideoxy-<scp>l</scp>-ascorbic Acid
  作者：Silvana Raić-Malić、Draženka Svedružić、Tatjana Gazivoda、Andreja Marunović、Antonija Hergold-Brundić、Ante Nagl、Jan Balzarini、Erik De Clercq、Mladen Mintas

  DOI：10.1021/jm0009540

  日期：2000.12.1

  The new pyrimidine derivatives of 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid (8-10) were synthesized by condensation of uracil and its 5-fluoro- and 5-trifluoromethyl-substituted derivatives with 4-(5,6-epoxypropyl)-2,3-O,O-dibenzyl-L-ascorbic acid (7), while pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-L-ascorbic acid (14-17) with free C-2' and C-3' hydroxy groups in the lactone ring were obtained by debenzylation of 11-13 with boron trichloride. Z-Configuration of the C4'=C5' double bond and position of the benzyl group in the lactone ring of 14 were deduced from their H-1 and C-13 NMR spectra and connectivities in COSY, ROESY, and HMBC spectra. The exact stereostructure of 13 was confirmed by its X-ray crystal structure analysis. Of all the compounds in the series, compound 16 containing a 5-fluoro-substituted uracil ring showed the most significant antitumor activities against murine leukemia L1210/0 (IC50 = 1.4 mug/mL), murine mammary carcinoma FM3A/0 (IC50 = 0.78 mug/mL), and, to a lesser extent, human T-lymphocyte cells Molt4/C8 (IC50 = 31.8 mug/mL) and CEM/0 cell lines (IC50 = 20.9 mug/mL).
• Novel Pyrimidine and Purine Derivatives of <scp>l</scp>-Ascorbic Acid:  Synthesis and Biological Evaluation
  作者：Silvana Raić-Malić、Antonija Hergold-Brundić、Ante Nagl、Mira Grdiša、Krešimir Pavelić、Erik De Clercq、Mladen Mintas

  DOI：10.1021/jm991017z

  日期：1999.7.1

  The novel pyrimidine derivatives 1-6 of 2,3-dibenzyl-4,5-didehydro-5,6-dideoxy-L-ascorbic acid were synthesized by the condensation of pyrimidine bases with 5,6-diacetyl-2,3-dibenzyl-L-ascorbic acid (DDA). Both N-9 (7) and N-7 (8) regioisomers were obtained in the reaction of 6-chloropurine with 5-acetyl-6-bromo-2,3-dibenzyl-L-ascorbic acid (ABDA), while the reaction of 6-(N-pyrrolyl)purine with ABDA afforded exclusively the N-9 isomer 9. Structures of all newly prepared compounds were deduced from the chemical shifts in H-1 and C-13 NMR spectra, as well as connectivities in 2D homo- and heteronuclear correlation spectra. An unambiguous proof of the structure and conformation of 7 was obtained by X-ray crystallographic analysis. Compounds 1-9 were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), murine leukemia (L1210/0), murine mammary carcinoma (FM3A), and human T-lymphocytes (Molt4/C8 and CEM/0), as well as antiviral activities against varicella-zoster virus (TK(+)VZV and TK(-)VZV) and cytomegalovirus (CMV). The compound 6 containing a trifluoromethyl-substituted uracil ring exhibited marked antitumor activity. The N-7-substituted purine regioisomer 8 had greater inhibitory effects on the murine L1210/0 and human CEM/0 cell lines than the N-9 isomer 7. Compound 9 with the B-purine-substituted pyrrolo moiety had a more pronounced selective cytostatic activity against human (Molt4/C8 and CEM-0) cell lines than murine (L1210/0 and FM3A/O) and human (MiaPaCa2, MCF7, HeLa, and Hep2) tumor cell lines and normal fibroblasts (Hef522). The compound 6 exhibited the most potent antiviral activities against TK(+)VZV, TK(-)VZV, and CMV, albeit at concentrations that were only slightly lower than the cytotoxic concentrations.
• The new 5- or 6-azapyrimidine and cyanuric acid derivatives of l-ascorbic acid bearing the free C-5 hydroxy or C-4 amino group at the ethylenic spacer: CD-spectral absolute configuration determination and biological activity evaluations
  作者：K. Wittine、M. Stipković Babić、M. Košutić、M. Cetina、K. Rissanen、S. Kraljević Pavelić、A. Tomljenović Paravić、M. Sedić、K. Pavelić、M. Mintas

  DOI：10.1016/j.ejmech.2011.03.066

  日期：2011.7

  6-azauracil (17) and cyanuric acid (21) derivatives of l-ascorbic acid bearing free amino group at ethylenic spacer existed as a racemic mixture of enantiomers, whereas L-ascorbic derivatives containing the C-5 substituted hydroxy group at the ethylenic spacer were obtained in (4R, 5S) enantiomeric form. The stereochemistry of 6-azauracil derivative of l-ascorbic acid (13) was confirmed by X-ray crystal structure

  我们对新颖类型胞嘧啶和5-氮杂胞嘧啶（的合成报告19），尿嘧啶和6-氮尿嘧啶（13 - 18和氰尿酸（）19 - 22）的衍生物升抗坏血酸，以及它们的抑制细胞生长的人体恶性肿瘤细胞系与肝癌细胞活性的评价。它们对人正常成纤维细胞（WI38）的细胞毒性作用。CD谱分析表明，胞嘧啶（5和6），尿嘧啶（14 - 16），6-氮尿嘧啶（17），氰尿酸（21）的衍生物升-在烯键间隔基上带有游离氨基的抗坏血酸以对映异构体的外消旋混合物的形式存在，而在烯键间隔基上含有C -5取代羟基的L-抗坏血酸衍生物以（4 R， 5 S）对映体形式获得。通过X射线晶体结构分析证实了1-抗坏血酸（13）的6-氮杂尿嘧啶衍生物的立体化学。这些分子通过一个N–H⋯O氢键，两个C–H⋯O氢键和两个C–H⋯π相互作用自组装成三维框架。细胞抑制活性评估表明化合物对测试的细胞系没有显示出明显的抗增殖作用。但是，l的胞嘧啶衍生物-含有C