2'-deoxy-5-(pentafluoroethyl)uridine | 84500-36-7

• 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: 2'-deoxy-5-(pentafluoroethyl)uridine
• 英文别名: 5-(pentafluoroethyl)-2'-deoxyuridine；5-pentafluoroethyl-2′-deoxyuridine；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(1,1,2,2,2-pentafluoroethyl)pyrimidine-2,4-dione
• CAS: 84500-36-7
• 化学式: C₁₁H₁₁F₅N₂O₅
• 分子量: 346.211
• InChiKey: HJHNQOOYBACTPQ-RRKCRQDMSA-N

物化性质

• 密度：
  1.669±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  三乙基碳酸氢铵缓冲液 、 2'-deoxy-5-(pentafluoroethyl)uridine 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 、 三正丁胺 、 三丁基焦磷酸铵 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 0.33h， 以10%的产率得到
  参考文献：
  名称：

  全氟烷基化DNA的酶促合成

  摘要：

  合成了胸苷类似物5-三氟甲基-，5-五氟乙基-和5-（七氟-正丙基）-2'-脱氧尿苷，并将其转化为相应的5'-三磷酸酯1a – c。进行DNA聚合酶催化的引物延伸反应，将这些修饰的核苷酸掺入DNA以产生全氟烷基化的核酸。尽管单个修饰的核苷酸被酶促地掺入并进一步延伸，与天然TTP十分相似，但是多重修饰的核酸的酶促合成仅在每四个碱基进行修饰的情况下才是最初可行的。但是，由于修饰的dUTP对DNA聚合酶的影响随所用酶的不同而有很大差异，Therminator DNA聚合酶擅长掺入11个相邻的5-trifluoromethyl-2'-deoxyuridine部分。

  DOI：

  10.1016/j.bmc.2009.03.063
• 作为产物：
  描述：

  2-脱氧尿苷 在 吡啶 、 盐酸 、 六甲基磷酰三胺 、 mercury(II) diacetate 、 碘 、 sodium acetate 、 铜 作用下， 以 甲醇 为溶剂， 反应 51.5h， 生成 2'-deoxy-5-(pentafluoroethyl)uridine
  参考文献：
  名称：

  Synthesis and biological activity of 5-(trifluoromethyl)- and 5-(pentafluoroethyl)pyrimidine nucleoside analogs

  摘要：

  Various 5-substituted perfluoroalkylpyrimidine nucleoside analogues have been synthesized, and their biological activity against L1210, S-180, Vero cells, and herpes simplex virus type 1 (HSV-1) was evaluated. The 5-trifluoromethyl derivatives, 7 and 9, showed significant antiviral activity against HSV-1 with ED50 values of 7 and 5 microM, respectively. In addition, the unblocked nucleoside 9 was found to be about 64-fold less toxic to the host Vero cells and gave a favorable therapeutic index of 64 against HSV-1 in vitro.

  DOI：

  10.1021/jm00358a028

文献信息

• “Ligandless” Pentafluoroethylation of Unactivated (Hetero)aryl and Alkenyl Halides Enabled by the Controlled Self-Condensation of TMSCF₃-Derived CuCF₃
  作者：Jordi Mestre、Sergio Castillón、Omar Boutureira

  DOI：10.1021/acs.joc.9b02001

  日期：2019.12.6

  Pentafluoroethylation of unactivated C(sp2)-X bonds (X = I, Br) using a storable, "ligandless" CuC2F5 reagent prepared by controlled self-condensation of ready available TMSCF3-derived CuCF3 has been developed. A thorough analysis by 19F NMR and ESI-MS revealed the nature of this reagent in solution. The operational simplicity and robustness of this system enables the efficient, late-stage incorporation

  已经开发出了一种可活化的，“无配体的” CuC2F5试剂对未活化的C（sp2）-X键（X = I，Br）进行五氟乙基化，该试剂通过可控的自发TMSCF3衍生的CuCF3的自缩合制备。通过19 F NMR和ESI-MS进行的彻底分析揭示了该试剂在溶液中的性质。该系统的操作简单性和鲁棒性使C2F5单元可以高效，后期地并入各种（杂）芳基和复杂的烯基卤化物（如糖基，核苷和核碱基）中。
• Direct perfluoroalkylation including trifluoromethylation of aromatics with perfluoro carboxylic acids mediated by xenon difluoride
  作者：Yoo Tanabe、Noritada Matsuo、Nobuo Ohno

  DOI：10.1021/jo00254a033

  日期：1988.9
• [EN] PYRIMIDINE NUCLEOSIDES<br/>[FR] NUCLEOSIDES DE PYRIMIDINE
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：WO1997006178A1

  公开（公告）日：1997-02-20

  (EN) Pyrimidine nucleoside derivatives of formula (I), wherein R1 to R8 each individually represent hydrogen, halogen, cyano, lower alkyl, halo-lower alkyl, lower alkoxy, lower cycloalkyl or aryl; or R1 and R2 together or R2 and R3 together or R3 and R4 together represent a fused benzene ring; R9 represents hydrogen or lower alkyl; R10 represents hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl-lower alkyl, lower cycloalkyl-lower alkyl, acyl, 2-pyrrolidinylcarbonyl or a group of the formula -C(O)-CH(R12)-NH2; R11 represents halogen, lower alkyl, halo-lower alkyl or lower cycloalkyl; R12 represents hydrogen, lower alkyl, aryl-lower alkyl, lower alkylthio-lower alkyl, amino-lower alkyl or (4-imidazolyl)-lower alkyl; W represents CH2, C(O) or C(S); X represents CH2 or O; Y represents hydrogen, fluorine or hydroxy; Z represents C(R13)(R14), O, S, SO, SO2, Si(R15)(R16) or N(R17); R13 and R14 each represent hydrogen, lower alkyl, halo-lower alkyl, aryl or aryl-lower alkyl or R13 and R14 together represent lower alkylene; R15 and R16 each represent lower alkyl; and R17 represents lower alkyl, and pharmaceutically acceptable salts of those compounds of formula (I) which are basic inhibit viral thymidine kinase and are useful as antiviral agents.(FR) La présente invention se rapporte à des dérivés de nucléosides de pyrimidine de formule (I), dans laquelle R1 à R8 représentent chacun individuellement hydrogène, halogène, cyano, alkyle inférieur, halo-alkyle inférieur, alkoxy inférieur, cycloalkyle inférieur ou aryle; ou R1 et R2 ensemble ou R2 et R3 ensemble ou R3 et R4 ensemble représentent un cycle condensé de benzène; R9 représente hydrogène ou alkyle inférieur; R10 représente hydrogène, alkyle inférieur, alkényle inférieur, alkynyle inférieur, aryle-alkyle inférieur, cycloalkyle inférieur-alkyle inférieur, acyle, 2-pyrrolidinylcarbonyle ou un groupe ayant pour formule -C(O)-CH(R12)-NH2; R11 représente halogène, alkyle inférieur, halo-alkyle inférieur ou cycloalkyle inférieur; R12 représente hydrogène, alkyle inférieur, aryle-alkyle inférieur, alkylthio inférieur-alkyle inférieur, amino-alkyle inférieur ou (4-imidazolyl)-alkyle inférieur; W représente CH2, C(O) ou C(S); X représente CH2 ou O; Y représente hydrogène, fluor ou hydroxy; Z représente C(R13)(R14), O, S, SO, SO2, Si(R15)(R16) ou N(R17); R13 et R14 représentent chacun hydrogène, alkyle inférieur, halo-alkyle inférieur, aryle ou aryle-alkyle inférieur ou R13 et R14 représentent ensemble alkylène inférieur; R15 et R16 représentent chacun alkyle inférieur; et R17 représente alkyle inférieur. Ces composés de formule (I) ainsi que leurs sels pharmaceutiquement acceptables, qui sont basiques, inhibent la thymidine kinase virale et sont utiles en tant qu'agents antiviraux.
• Enzymatic synthesis of perfluoroalkylated DNA
  作者：Bastian Holzberger、Andreas Marx

  DOI：10.1016/j.bmc.2009.03.063

  日期：2009.5

  Thymidine analogues 5-trifluoromethyl-, 5-pentafluoroethyl- and 5-(heptafluoro-n-propyl)-2′-deoxyuridines were synthesised and converted into the corresponding 5′-triphosphates 1a–c. Performing DNA polymerase-catalyzed primer extension reactions these modified nucleotides were incorporated into DNA to create perfluoroalkylated nucleic acids. Although single modified nucleotides were enzymatically incorporated

  合成了胸苷类似物5-三氟甲基-，5-五氟乙基-和5-（七氟-正丙基）-2'-脱氧尿苷，并将其转化为相应的5'-三磷酸酯1a – c。进行DNA聚合酶催化的引物延伸反应，将这些修饰的核苷酸掺入DNA以产生全氟烷基化的核酸。尽管单个修饰的核苷酸被酶促地掺入并进一步延伸，与天然TTP十分相似，但是多重修饰的核酸的酶促合成仅在每四个碱基进行修饰的情况下才是最初可行的。但是，由于修饰的dUTP对DNA聚合酶的影响随所用酶的不同而有很大差异，Therminator DNA聚合酶擅长掺入11个相邻的5-trifluoromethyl-2'-deoxyuridine部分。
• Synthesis and biological activity of 5-(trifluoromethyl)- and 5-(pentafluoroethyl)pyrimidine nucleoside analogs
  作者：Tai Shun Lin、You Song Gao

  DOI：10.1021/jm00358a028

  日期：1983.4

  Various 5-substituted perfluoroalkylpyrimidine nucleoside analogues have been synthesized, and their biological activity against L1210, S-180, Vero cells, and herpes simplex virus type 1 (HSV-1) was evaluated. The 5-trifluoromethyl derivatives, 7 and 9, showed significant antiviral activity against HSV-1 with ED50 values of 7 and 5 microM, respectively. In addition, the unblocked nucleoside 9 was found to be about 64-fold less toxic to the host Vero cells and gave a favorable therapeutic index of 64 against HSV-1 in vitro.