2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-fluorouracil | 43176-57-4

• 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: 2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-fluorouracil
• 英文别名: 2,2’-anhydro-5-fluorouridine；2,2'-anhydro-5-fluorouridine；(3aS)-7-fluoro-3c-hydroxy-2t-hydroxymethyl-(3ar,9ac)-2,3,3a,9a-tetrahydro-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-6-one；5-fluoro-arabino-2,2'-anhydro-uridine；2,2'-Anhydro-1-(β-D-arabinofuranosyl)-5-fluor-uracil；5-Fluor-O^2,2'-anhydrouridin；6H-Furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-6-one, 7-fluoro-2,3,3a,9a-tetrahydro-3-hydroxy-2-(hydroxymethyl)-, (2R,3R,3aS,9aR)-；(2R,4R,5R,6S)-11-fluoro-5-hydroxy-4-(hydroxymethyl)-3,7-dioxa-1,9-diazatricyclo[6.4.0.02,6]dodeca-8,11-dien-10-one
• CAS: 43176-57-4
• 化学式: C₉H₉FN₂O₅
• 分子量: 244.179
• InChiKey: IKFXNFGQZPQQSR-MNCSTQPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  91.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-fluorouracil 在 水 作用下， 以 乙腈 为溶剂， 反应 13.0h， 生成 1-(5-磷酰-beta-D-阿拉伯呋喃糖基)-5-氟尿嘧啶
  参考文献：
  名称：

  Interaction of 1-(5-phospho-.beta.-D-arabinofuranosyl)-5-substituted-uracils with thymidylate synthetase: mechanism-based inhibition by 1-(5-phospho-.beta.-D-arabinofurosyl)-5-fluorouracil

  摘要：

  A number of 1-(5-phospho-beta-D-arabinosyl)-5-substituted-uracils (ara-UMP's) have been examined as inhibitors of dTMP synthetase. As reversible inhibitors, all were substantially less potent than their 2'-deoxyribosyl counterparts. In the presence of 5,10-methylenetetrahydrofolate (CH2-H4folate), ara-FUMP caused a first-order, time-dependent inactivation of the enzyme. At 0 degrees C, kinetic studies indicated a reversible Kd of 3.6 micro M for the ara-FUMP-CH2-H4folate complex, and k = 0.22 min-1 for the subsequent inactivation. Spectral studies of the complex and its behavior toward protein denaturants demonstrate that its structure and stoichiometry are directly analogous to those which have previously been described for FdUMP. The significance of this finding with regard to prodrugs of ara-FU and the potential of ara-FU as a chemotherapeutic agent are discussed.

  DOI：

  10.1021/jm00142a008
• 作为产物：
  描述：

  5-氟尿嘧啶核苷 在 碳酸二苯酯 、 碳酸氢钠 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 0.67h， 以39%的产率得到2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-fluorouracil
  参考文献：
  名称：

  亚基因组HCV复制子系统中一系列d和1-2'-deoxy-2'-氟核糖核苷的合成及抗病毒活性。

  摘要：

  基于发现（2'R）-d-2'-deoxy-2'-氟胞苷作为有效的抗丙型肝炎病毒（HCV）剂，一系列d-和1-2'-deoxy-2'合成了具有5-和/或4-位修饰的-氟核糖核苷，并评估了其抗HCV和牛病毒性腹泻病毒（BVDV）的体外活性。合成中的关键步骤，即2'-氟基团的引入是通过用氟化氢-吡啶或氟化钾对2,2'-脱水核苷进行氟化，或用DAST对阿拉伯糖核苷进行氟化来实现的。在合成的27个类似物中，只有5-氟化合物，即（2'R）-d-2'-deoxy-2'，5-difluorocytidine（13），显示出有效的抗HCV活性和对核糖体RNA的毒性。用硫醇基取代4-氨基会导致活性降低，而4-甲硫基取代的类似物（25）会抑制核糖体RNA。由于N（4）-羟基胞嘧啶核苷（NHC）先前显示出有效的抗HCV活性，我们将N（4）-羟基和2'-氟的两个功能合并为一个分子，得到（2'R）-d -2'-脱氧-

  DOI：

  10.1016/j.bmc.2004.12.011

文献信息

• A simple and efficient synthesis of puromycin, 2,2′-anhydro-pyrimidine nucleosides, cytidines and 2′,3′-anhydroadenosine from 3′,5′-<i>O</i>-sulfinyl<i>Xylo</i>-nucleosides
  作者：Ken-ichi Takatsuki、Sumito Ohgushi、Shigeo Kohmoto、Keiki Kishikawa、Makoto Yamamoto

  DOI：10.1080/15257770600725929

  日期：2006.8

  antibiotics, puromycin and 3 ′-amino-3 ′-deoxy-N 6,N 6-dimethyladenosine 11 was achieved by utilizing the cyclic sulfite 6a of the xylo-3 ′,5 ′-dihydroxy group as a new protective group. The key synthetic step is the deprotection of the sulfite moiety through the intramolecular cyclization of 2-α-carbamate 7. In a similar manner, 2,2 ′-anhydro-pyrimidine nucleosides 15, ribo-cytidines 17 and 2 ′,3 ′-anhydroadenosine

  利用xylo-3′，5′-二羟基的环状亚硫酸盐6a作为新的保护基，合成了嘌呤霉素和3′-氨基-3′-脱氧-N 6，N 6-二甲基腺苷11。关键的合成步骤是通过2-α-氨基甲酸酯7的分子内环化作用对亚硫酸盐部分进行脱保护。类似地，2,2'-脱水嘧啶核苷15，核糖胞苷17和2'，3'-分别由相应的亚硫酸盐4、5和6b高产率地制备了脱水腺苷14。
• Holy,A.; Cech,D., Collection of Czechoslovak Chemical Communications, 1974, vol. 39, p. 3157 - 3167
  作者：Holy,A.、Cech,D.

  DOI：——

  日期：——
• Synthesis and anti-viral activity of a series of d- and l-2′-deoxy-2′-fluororibonucleosides in the subgenomic HCV replicon system
  作者：Junxing Shi、Jinfa Du、Tianwei Ma、Krzysztof W. Pankiewicz、Steven E. Patterson、Phillip M. Tharnish、Tamara R. McBrayer、Lieven J. Stuyver、Michael J. Otto、Chung K. Chu

  DOI：10.1016/j.bmc.2004.12.011

  日期：2005.3.1

  of the N(4)-hydroxyl and the 2'-fluoro into one molecule, resulting (2'R)-d-2'-deoxy-2'-fluoro-N(4)-hydroxycytidine (23). However, this nucleoside showed neither anti-HCV activity nor toxicity. All the l-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot always predict anti-HCV activity.

  基于发现（2'R）-d-2'-deoxy-2'-氟胞苷作为有效的抗丙型肝炎病毒（HCV）剂，一系列d-和1-2'-deoxy-2'合成了具有5-和/或4-位修饰的-氟核糖核苷，并评估了其抗HCV和牛病毒性腹泻病毒（BVDV）的体外活性。合成中的关键步骤，即2'-氟基团的引入是通过用氟化氢-吡啶或氟化钾对2,2'-脱水核苷进行氟化，或用DAST对阿拉伯糖核苷进行氟化来实现的。在合成的27个类似物中，只有5-氟化合物，即（2'R）-d-2'-deoxy-2'，5-difluorocytidine（13），显示出有效的抗HCV活性和对核糖体RNA的毒性。用硫醇基取代4-氨基会导致活性降低，而4-甲硫基取代的类似物（25）会抑制核糖体RNA。由于N（4）-羟基胞嘧啶核苷（NHC）先前显示出有效的抗HCV活性，我们将N（4）-羟基和2'-氟的两个功能合并为一个分子，得到（2'R）-d -2'-脱氧-
• Interaction of 1-(5-phospho-.beta.-D-arabinofuranosyl)-5-substituted-uracils with thymidylate synthetase: mechanism-based inhibition by 1-(5-phospho-.beta.-D-arabinofurosyl)-5-fluorouracil
  作者：Chikao Nakayama、Yusuke Wataya、Daniel V. Santi、Mineo Saneyoshi、Tohru Ueda

  DOI：10.1021/jm00142a008

  日期：1981.10

  A number of 1-(5-phospho-beta-D-arabinosyl)-5-substituted-uracils (ara-UMP's) have been examined as inhibitors of dTMP synthetase. As reversible inhibitors, all were substantially less potent than their 2'-deoxyribosyl counterparts. In the presence of 5,10-methylenetetrahydrofolate (CH2-H4folate), ara-FUMP caused a first-order, time-dependent inactivation of the enzyme. At 0 degrees C, kinetic studies indicated a reversible Kd of 3.6 micro M for the ara-FUMP-CH2-H4folate complex, and k = 0.22 min-1 for the subsequent inactivation. Spectral studies of the complex and its behavior toward protein denaturants demonstrate that its structure and stoichiometry are directly analogous to those which have previously been described for FdUMP. The significance of this finding with regard to prodrugs of ara-FU and the potential of ara-FU as a chemotherapeutic agent are discussed.