1-(2,3-dideoxy-3-fluoro-α-D-erythro-pentofuranosyl)-thymine | 116209-63-3

• 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: 1-(2,3-dideoxy-3-fluoro-α-D-erythro-pentofuranosyl)-thymine
• 英文别名: 1-[(2S,4S,5R)-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 116209-63-3
• 化学式: C₁₀H₁₃FN₂O₄
• 分子量: 244.223
• InChiKey: UXCAQJAQSWSNPQ-RNJXMRFFSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,3-dideoxy-3-fluoro-α-D-erythro-pentofuranosyl)-thymine 在 水合三氯化钌 、 potassium persulfate 、 potassium hydroxide 作用下， 反应 8.0h， 以46%的产率得到1-(3,4-didehydro-2,3-dideoxy-β-d-pentofuranosyl-4-carboxy)thymine
  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：

  O,O-二(三甲基甲硅烷基)胸苷 在 氢氧化钾 、 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 0.67h， 生成 1-(2,3-dideoxy-3-fluoro-α-D-erythro-pentofuranosyl)-thymine
  参考文献：
  名称：

  1-硫代戊呋喃糖苷与甲硅烷基化嘧啶碱基的-溴代琥珀酰亚胺活化反应：3'-叠氮基-3'-脱氧胸苷及其相关核苷类似物的合成

  摘要：

  3'-叠氮基-3'-脱氧胸苷，3'-氟-3'-脱氧胸苷及其2'-取代的衍生物和L-对映异构体是通过相应的苯基1-硫代呋喃呋喃糖苷与甲硅烷基化胸腺嘧啶的活化反应偶联而合成的与-溴琥珀酰亚胺。

  DOI：

  10.1016/s0040-4039(00)74337-1

文献信息

• Synthesis of 2′,3′-Dideoxy-3′-fluorothymidine Using Individual Anomers of 1,5-Di-<i>O</i>-benzoyl-2,3-dideoxy-3-fluoro-D-<i>erythro</i>-pentofuranose as Glycosylating Agents
  作者：Igor A. Mikhailopulo、Tamara I. Pricota、Nicolai E. Poopeiko、Tatjana V. Klenitskaya、Natalia B. Khripach

  DOI：10.1055/s-1993-25925

  日期：——

  A convenient preparation of α- and β-anomers of 1,5-di-O-benzoyl-2, 3-dideoxy-3-fluoro-D-erythro-pentofuranose is described. Each anomer is studied as the glycosylating agent in the reaction with bis-trimethylsilylated thymine in the presence of trimethylsilyl triflate. Under optimum conditions, 2′,3′-dideoxy-3′-fluorothymidine (FLT) and its α-anomer are isolated in 64 and 25% yields, respectively.

  描述了一种方便的制备1,5-二-O-苯甲酰基-2,3-去氧-3-氟-D-赤糖戊呋喃糖的α-和β-异构体的方法。每种异构体作为糖苷化试剂，与双三甲基硅基化胸腺嘧啶在三甲基硅基三氟甲磺酸的存在下进行反应。 在最佳条件下，2′,3′-去氧-3′-氟胸腺苷（FLT）及其α-异构体的产率分别为64%和25%。
• Methyl 5-0--butyldiphenylsilyl-2-deoxy-α β -d--pentofuranoside as a divergent intermediate for the synthesis of 3'-substituted-2',3'-dideoxynucleosides: synthesis of 3'-azido-3'-deoxythymidine, 3'-deoxy-3'-fluorothymidine and 3'-cyano-3'-deoxythymidine.
  作者：George W.J. Fleet、Jong Chan Son、Andrew E. Derome

  DOI：10.1016/s0040-4020(01)85850-6

  日期：1988.1

  The use of methyl 5-0--butyldiphenylsilyl-2-deoxy-α , β -D--pentofuranoside, prepared from D-xylose,as a divergent intermediate for the synthesis of 3'-substituted-2',3'-dideoxynucleosides is illustrated by its conversion into 3'-azido-3'-deoxythymidine, 3'-deoxy-3'-fluorothymidine and 3'-cyano-3'-deoxythymidine.

  由D-木糖制得的甲基5-0-丁基二苯基甲硅烷基-2-脱氧-α，β-D-五呋喃糖苷作为合成3'-取代的2'，3'-二脱氧核苷的发散中间体的用途通过将其转化为3'-叠氮基-3'-脱氧胸苷，3'-脱氧-3'-氟胸苷和3'-氰基-3'-脱氧胸苷来举例说明。
• 2‘-Chloro-2‘,3‘-dideoxy-3‘-fluoro-<scp>d</scp>-ribonucleosides:  Synthesis, Stereospecificity, Some Chemical Transformations, and Conformational Analysis
  作者：Igor A. Mikhailopulo、Tamara I. Pricota、Grigorii G. Sivets、Cornelis Altona

  DOI：10.1021/jo0340859

  日期：2003.7.1

  afforded 2',3'-didehydro-2',3'-dideoxy-2'-chloro-d-pentofuranosyl nucleosides as the principal products (47-81%) of the reaction, along with recovered starting nucleoside (11-33%) (Scheme 3). Easy HF elimination was also observed in the case of the 2'-azido-2',3'-dideoxy-3'-fluoro-beta-d-ribofuranosides of thymine (17) and adenine (20) (Scheme 3). The role of conformational peculiarities of 2'-chloro-2'

  5-O-苯甲酰基-2-氯-2,3-二脱氧-3-氟-β-d-呋喃核糖苷甲基的合成（5）及其作为全硅烷化胸腺嘧啶N（6）-苯甲酰腺嘌呤的糖基化剂的用途，描述了N（4）-苯甲酰基胞嘧啶（方案1）。将合成的2'-氯-2'，3'-二脱氧-3'-氟-d-核糖核苷转化为2'，3'-二脱氧-3'-氟-α-和-β-d-胸腺嘧啶（13a，b），腺嘌呤（14a，b）和胞苷（15a，b）的赤型-呋喃呋喃糖核苷，在α，α'-偶氮二异丁腈存在下，用氢化三丁基锡处理（方案2）。用1 M MeONa / MeOH在回流下处理2'-氯-2'，3'-二脱氧-3'-氟-d-核糖核苷1-5小时，得到2'，3'-二氢化-2'，3' -二脱氧-2' 反应的主要产物是-氯-d-戊呋喃糖基核苷（47-81％），以及回收的起始核苷（11-33％）（方案3）。在胸腺嘧啶（17）和腺嘌呤（20）的2'-叠氮基2'，3'-二脱氧氧基3'-氟-β
• Nucleoside derivatives
  申请人：Medivir Aktiebolag

  公开号：EP0352248A1

  公开（公告）日：1990-01-24

  L-ribofuranosyl nucleoside analogues of the formula wherein B is adenine, guanine, hypoxanthine, 2,6-diaminopurine or R¹ is H, F; R³ is H, OH, F, N₃, CN or R¹ and R² together constitute a chemical bond; R³ is OH or wherein n is 0, 1 or 2; R⁴ is OH, NH₂; R⁵ is H, CH₃ or C₂H₅,with certain provisos, in the form of a mixture of alpha and beta anomers or in the form of an alpha or beta anomer for use in therapy in pharmaceutical compositions for therapeutic or prophy­lactic treatment of infections caused by HIV-viruses, hepatitis B virus or herpes viruses.

  L-核糖呋喃核苷类似物的化学式，其中B为腺嘌呤，鸟嘌呤，次黄嘌呤，2，6-二氨基嘌呤或R¹为H，F; R³为H，OH，F，N₃，CN或R¹和R²共同构成化学键; R³为OH或其中n为0，1或2; R⁴为OH，NH₂; R⁵为H，CH₃或C₂H₅，在某些限制条件下，以α和β异构体的混合物形式或以α或β异构体的形式用于治疗药物组合物，用于治疗或预防由HIV病毒，乙型肝炎病毒或疱疹病毒引起的感染。
• Nucleosides and nucleoside analogues, pharmaceutical composition and processes for the preparation of the compounds
  申请人：Medivir Aktiebolag

  公开号：EP0516186A2

  公开（公告）日：1992-12-02

  A compound of a formula (I) wherein the radicals A, X, R² and R³ are defined as follows wherein R¹ is H, alkyl containing 1-3 carbon atoms, including cyclopropyl; -CH=CH₂; -CH=CH-CH₃; -CH₂-CH=CH₂; C≡CH X: (a) S (b) CH₂ R²:H; or R² constitutes together with R³ a carbon - carbon bond R³:H; F; Cl; Br; I; N₃; CN; C≡CH; OH; OCH₃; CH₂OH; whereby when R³ in formula I is F; Cl; Br; I; N₃; CN; C≡CH; OH; OCH₃ or CH₂OH it may have either cis-configuration or trans-configuration relative to the hydroxymethyl function at position 4', or R³ constitutes together with R² a carbon - carbon bond, and therapeutically acceptable salts thereof for use in therapy, in particular for the treatment of HIV infections.

  式 (I) 的化合物 其中自由基 A、X、R² 和 R³ 定义如下 其中 R¹ 是 H、含 1-3 个碳原子的烷基，包括环丙基；-CH=CH₂；-CH=CH-CH₃；-CH₂-CH=CH₂； C≡CH X: (a) S (b) CH₂ R²：H；或 R² 与 R³ 共同构成碳-碳键 R³:H；F；Cl；Br；I；N₃；CN；C≡CH；OH；OCH₃；CH₂OH； 当式 I 中的 R³ 为 F；Cl；Br；I；N₃；CN；C≡CH；OH；OCH₃或 CH₂OH，相对于 4'位的羟甲基官能团可具有顺式构型或反式构型，或 R³ 与 R² 一起构成碳-碳键，以及其治疗上可接受的盐类，用于治疗，特别是治疗 HIV 感染。