α-2'-deoxy-5-fluorouridine | 2968-28-7

• 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: α-2'-deoxy-5-fluorouridine
• 英文别名: 2'-deoxy-5-fluorouridine；α-2'-Deoxy-5-fluoruridin；α-2'-Desoxy-5-fluoruridin；α-5-Fluordesoxyuridin；1-(α-D-erythro-2-deoxy-pentofuranosyl)-5-fluoro-1H-pyrimidine-2,4-dione；1-(α-D-erythro-2-Desoxy-pentofuranosyl)-5-fluor-1H-pyrimidin-2,4-dion；5-Fluor-1-<2-desoxy-α-D-ribofuranosyl>-uracil；1-(α-D-2-Desoxy-ribofuranosyl)-5-fluor-uracil；5-fluoro-1-[(2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 2968-28-7
• 化学式: C₉H₁₁FN₂O₅
• 分子量: 246.195
• InChiKey: ODKNJVUHOIMIIZ-XVMARJQXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 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：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  α-2'-deoxy-5-fluorouridine 在 水合三氯化钌 、 potassium persulfate 、 potassium hydroxide 作用下， 反应 5.0h， 以31%的产率得到α-5-Fluordesoxyuridin-5'-carbonsaeure
  参考文献：
  名称：

  A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses

  摘要：

  Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'-didehydrothymidine (16) was most effective against DHBV, HBV and HCV. Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl group (17) did not affect the anti-HBV activity but greatly increased the anti-HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined with ribavirin without toxicity. The activity exhibited by a single agent towards both hepatitis viruses and no detectable in vitro cytotoxicity make this new class of compounds of interest. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.042
• 作为产物：
  描述：

  [(2R,3S,5S)-3-(4-chlorobenzoyl)oxy-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl 4-chlorobenzoate 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 α-2'-deoxy-5-fluorouridine
  参考文献：
  名称：

  5-取代的2'-脱氧尿苷异头体的立体选择性合成

  摘要：

  研究了5-取代的2,4-双(三甲基甲硅烷氧基)嘧啶与3,5-双(Op-氯苯甲酰基)-2-脱氧-α-D-呋喃核糖基氯的取代反应。在对硝基苯酚的存在下，β端基异构体立体选择性地形成，而有机碱的加入导致α端基异构体的立体选择性形成。反应的立体选择性取决于二甲硅烷基嘧啶的 5 位取代基、添加剂和每种试剂的浓度。5-取代的2'-脱氧-尿苷的α和β异头通过5-取代3',5'-二-O-(对-氯苯甲酰基)-2'-脱氧尿苷的α和β异头脱酰化合成。

  DOI：

  10.1246/bcsj.60.2073

文献信息

• Preparation, antibacterial effects and enzymatic degradation of 5-fluorouracil nucleosides
  作者：Beatrice Schwarz、Dieter Cech、Antonín Holý、Jan Škoda

  DOI：10.1135/cccc19803217

  日期：——

  Reaction of perbenzoylated aldopentafuranosyl derivatives of uracil with fluorine in acetic acid afforded perbenzoylated 5-fluorouracil nucleosides. Their methanolysis gave the following free nucleosides of 5-fluorouracil: β-D-ribofuranoside (Id), 2-deoxy-β-D-ribofuranoside (IId), their enantiomers VIII and IX, α-D-ribofuranoside (XIII), 2-deoxy-α-D-ribofuranoside (XV), β-D-arabinofuranoside (IV) and its L-enantiomer X, β-D-xylofuranoside (V) and its α-D-anomer XI, α-L-lyxofuranoside (VI) and 2-deoxy-α-L-lyxofuranoside (VII) and the enantiomers of the latter two compounds, XII and XIV, respectively. Analogously were obtained 5-deoxy-β-D-ribofuranoside (III), β-D-ribopyranoside (XVI) and 1-(S)-(2,3-dihydroxypropyl)-5-fluorouracil (XVIIc). 1-Allyl-5-fluorouracil (XVIII) was prepared by reaction of allyl bromide with 2,4-bis(trimethylsilyloxy)-5-fluoropyrimidine. The cell-free extract from Escherichia coli cleaves all the 5-fluorouracil nucleosides in which the nucleoside carbon atom has the R-configuration and the 3'-hydroxyl of the sugar moiety is in trans-relation to the base. Compounds which have not these structural features are resistant. Besides nucleosides which on enzymatic cleavage afford 5-fluorouracil, also the non-cleavable 1-(2-deoxy-β-L-ribofuranosyl)-5-fluorouracil (IX), 1-(2-deoxy-α-D-ribofuranosyl)-5-fluorouracil (XV) and 1-(2-deoxy-α-D-lyxofuranosyl)-5-fluorouracil (XIV) exhibit an antibacterial effect towards E. coli (ID₅₀ 1.0-2.5 . 10^-5 M). This effect can be reversed by 2'-deoxyuridine but not by thymidine.

  在冰乙酸中，尿嘧啶的苄酰化醛基五糖衍生物与氟反应生成了苄酰化的5-氟尿嘧啶核苷。它们的甲醇解产生了以下的游离5-氟尿嘧啶核苷：β-D-核糖呋喃苷（Id）、2-脱氧-β-D-核糖呋喃苷（IId）、它们的对映异构体VIII和IX、α-D-核糖呋喃苷（XIII）、2-脱氧-α-D-核糖呋喃苷（XV）、β-D-阿拉伯呋喃苷（IV）及其L-对映体X、β-D-木糖呋喃苷（V）及其α-D-异构体XI、α-L-吕糖呋喃苷（VI）和2-脱氧-α-L-吕糖呋喃苷（VII）以及后两种化合物的对映体XII和XIV。类似地获得了5-脱氧-β-D-核糖呋喃苷（III）、β-D-核糖吡喃苷（XVI）和1-(S)-(2,3-二羟基丙基)-5-氟尿嘧啶（XVIIc）。1-丙烯基-5-氟尿嘧啶（XVIII）是通过丙烯基溴和2,4-双(三甲基硅氧基)-5-氟嘧啶反应制备的。大肠杆菌的细胞提取物可裂解所有5-氟尿嘧啶核苷，其中核苷碳原子具有R-构型，糖基的3'-羟基与碱基呈反式关系。不具备这些结构特征的化合物是抗性的。除了在酶解时产生5-氟尿嘧啶的核苷外，还有不可裂解的1-(2-脱氧-β-L-核糖呋喃基)-5-氟尿嘧啶（IX）、1-(2-脱氧-α-D-核糖呋喃苷)-5-氟尿嘧啶（XV）和1-(2-脱氧-α-D-吕糖呋喃苷)-5-氟尿嘧啶（XIV）对大肠杆菌表现出抗菌作用（ID50为1.0-2.5 x 10^-5 M）。这种效应可以被2'-脱氧尿苷而不是胸苷逆转。
• 2-Thio derivatives of dUrd and 5-fluoro-dUrd and their 5'-monophosphates: synthesis, interaction with tumor thymidylate synthase, and in vitro antitumor activity
  作者：Maria Bretner、Tadeusz Kulikowski、Jolanta M. Dzik、Malgorzata Balinska、Wojciech Rode、David Shugar

  DOI：10.1021/jm00075a016

  日期：1993.11

  deblocked with MeOH-NH3 to give the desired free anomeric nucleoside pairs 1, 5 and 3, 7, respectively. These were selectively converted to the corresponding 5'-monophosphates 2, 6 and 4, 8, with the aid of the wheat shoot phosphotransferase system. Conformations of the nucleosides 1, 3, 5, 7 are deduced from 1H NMR spectra, and circular dichroism spectra for nucleotide anomeric pairs 2, 6 and 4, 8 are reported

  5-氟-2-硫尿嘧啶（11）的方便合成是基于5-氟-2-硫胞嘧啶（9）的水解脱氨基。路易斯酸催化二-TMS-5-氟-2-硫氧嘧啶（13）或二-TMS-2-硫氧嘧啶（14）与2-脱氧-3,5-二-对甲苯基-D-呋喃呋喃糖酰氯的缩合反应（15）生成3'，5'-甲苯化2'-脱氧-5-氟-2-硫代尿苷（16和18）或2'-脱氧-2-硫代尿苷（17的β-和α-端基异构体的混合物和19），将它们各自用MeOH-NH 3解封闭，分别得到所需的游离异头核苷对1、5和3、7。在小麦芽磷酸转移酶系统的帮助下，将它们选择性地转化为相应的5'-单磷酸酯2、6和4、8。由1H NMR光谱推导出核苷1、3、5、7的构象，以及核苷酸异头对2的圆二色性光谱2 报告了6和4、8。尽管beta-2-thio-dUMP（4）是一个很好的底物（Km约为10（-5）M），但是beta-5-fluoro-2-thio-dUMP（2）
• Antiviral agents
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0457326A1

  公开（公告）日：1991-11-21

  Nucleoside compounds of the formula wherein:    B is a purine or a pyrimidine;    X and X' are H, OH or F, provided that at least one is H;    Y and Y' are H, OH, OCH₃ or F, provided that at least one is H;    Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is where n is zero, one, two or three; and Z' is N₃ or OCH₃;    provided that whenX' and Y' are OH and Z' is N₃, B is not cytosine, whenX' and Y' are OH and Z' is OCH₃, B is not uracil, adenine or cytosine, and whenZ' is N₃, X' is H, and Y' is H, OH, OCH₃, or F, B is not purine, cytosine, uracil, or thymine; and the pharmaceutically acceptable esters, ethers and salts thereof, have been found to have potent antiviral activity with a high therapeutic ratio.

  式中的核苷化合物 其中 B 是嘌呤或嘧啶； X 和 X'是 H、OH 或 F，但至少有一个是 H； Y 和 Y'是 H、OH、OCH₃ 或 F，但至少有一个是 H； Y' 和 Z 共同形成环磷酸酯，条件是 Y 是 H；或 Z 是 其中 n 为 0、1、2 或 3；以及 Z' 是 N₃ 或 OCH₃； 条件是 当 X' 和 Y' 为 OH 且 Z' 为 N₃ 时，B 不是胞嘧啶、 当X'和Y'为OH且Z'为OCH₃时，B不是尿嘧啶、腺嘌呤或胞嘧啶，以及 当 Z' 是 N₃，X' 是 H，Y' 是 H、OH、OCH₃ 或 F 时，B 不是嘌呤、胞嘧啶、尿嘧啶或胸腺嘧啶； 及其药学上可接受的酯、醚和盐，已被发现具有强效抗病毒活性和高治疗比。
• Materials and methods for suppressing and/or treating bacterial infections and related symptoms
  申请人：Indiana University Research and Technology Corporation

  公开号：US10933075B2

  公开（公告）日：2021-03-02

  Various aspects and embodiments disclosed herein relate generally to the modelling, treatment, reducing resistence to the treatment, prevention, and diagnosis of diseases/symptoms induced by infectious bacteria. Embodiments include methods of treating a bacterial infection, comprising the steps of: providing to a patient diagnosed with staphylococcal infection at least one therapeutically effective dose of a compound having an anti-virulence effect.

  本文公开的各种方面和实施方案一般涉及由传染性细菌诱发的疾病/症状的建模、治疗、降低对治疗的抵抗力、预防和诊断。实施方案包括治疗细菌感染的方法，包括以下步骤：向诊断为葡萄球菌感染的患者提供至少一种治疗有效剂量的具有抗病毒作用的化合物。
• Direct Synthesis of α- and β-2′-Deoxynucleosides with Stereodirecting Phosphine Oxide via Remote Participation
  作者：Xintong Tang、Yueer Zhou、Yingjie Wang、Yetong Lin、Shuheng Pan、Qianwei Che、Jinpeng Sang、Ziming Gao、Weiting Zhang、Yuanyuan Wang、Guolong Li、Longwei Gao、Zhimei Wang、Xudong Yang、Ao Liu、Suyu Wang、Biao Yu、Peng Xu、Zhe Wang、Zhaolun Zhang、Peng Yang、Weijia Xie、Haopeng Sun、Wei Li

  DOI：10.1021/jacs.4c01780

  日期：2024.3.27

  participating group to enable highly antifacial N-glycosylation. This proposed remote participation mechanism is supported by our first characterization of an important 1,5-briged P-heterobicyclic intermediate via variable-temperature NMR spectroscopy. Interestingly, antiproliferative assays led to a α-2′-deoxynucleoside with IC50 values in the low micromole range against central nervous system tumor cell lines

  2′-脱氧核苷及其类似物在药物开发中发挥着至关重要的作用，但其制备仍然是一个重大挑战。先前的研究主要集中在具有天然β构型的β-2′-脱氧核苷。事实上，它们的异构体α-2′-脱氧核苷也表现出多种生物活性和更好的代谢稳定性。在此，我们报道使用远程定向二苯基膦酰基（DPP）基团可以高产率和立体选择性地制备α-和β-2'-脱氧核苷。使用易于获得的 3,5-二-ODPP 供体制备 α-2'-脱氧核苷特别有效。在我们之前的同步面部O-糖基化研究中，氧化膦部分不是充当2-（二苯基膦酰基）乙酰基（DPPA）基团上的氢键受体，而是充当远程参与基团，以实现高度反面部的N-糖基化。这种提出的远程参与机制得到了我们通过变温核磁共振波谱对重要的 1,5-桥P杂双环中间体的首次表征的支持。有趣的是，抗增殖测定导致α-2'-脱氧核苷对中枢神经系统肿瘤细胞系SH-SY5Y和LN229的IC 50值在低微摩尔范围内，而其β-端基异构体在100