β-(L)-2’,3’-dideoxy-2’-fluoro-thymidine

• 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: β-(L)-2’,3’-dideoxy-2’-fluoro-thymidine
• 英文别名: 1-[(2S,3S,5R)-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₀H₁₃FN₂O₄
• 分子量: 244.223
• InChiKey: NPHYUIHLLMXOFR-FJXKBIBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 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

• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 氟化铵 、 三氟甲磺酸三甲基硅酯 作用下， 以 甲醇 为溶剂， 生成 β-(L)-2’,3’-dideoxy-2’-fluoro-thymidine
  参考文献：
  名称：

  A Completely Diastereoselective Electrophilic Fluorination of a Chiral, Noncarbohydrate Sugar Ring Precursor:  Application to the Synthesis of Several Novel 2‘-Fluoronucleosides

  摘要：

  A new and completely diastereoselective method for the introduction of fluorine into a noncarbohydrate sugar ring precursor has been developed. The use of N-fluorodibenzenesulfonimide (5) for the electrophilic fluorination of chiral lactone 4, which is derived from L-glutamic acid, yields the key intermediate 6. This is transformed into an anomeric acetate 8 and is used for the synthesis of a number of novel alpha-2'-fluoronucleosides. Since glutamic acid is used as the synthetic starting material, the L enantiomer may also be synthesized simply by using D-glutamic acid. The incorporation of fluorine into the 2' position of the nucleoside provides several advantages including acid stability of the anomeric bond and general resistance to oxidative metabolism. Further, fluorine is a close mimic of hydroxyl groups in size and polarity and in its ability to act as a hydrogen bond acceptor. This may aid in the recognition of these nucleosides by the enzymes involved in nucleoside activation.

  DOI：

  10.1021/jo9717898

文献信息

• 2′-fluoronucleosides
  申请人：Schinazi Raymond F.

  公开号：US09180138B2

  公开（公告）日：2015-11-10

  2′-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein Base is a purine or pyrimidine base; R1 is OH, H, OR3, N3, CN, halogen, CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy; R2 is H, phosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving benzyl, a lipid, an amino acid, peptide, or cholesterol; and R3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group; or a pharmaceutically acceptable salt thereof.

  披露了用于治疗乙型肝炎感染、丙型肝炎感染、艾滋病毒和异常细胞增殖（包括肿瘤和癌症）的2'-氟核苷类化合物。这些化合物具有以下一般化学式： 其中 Base是嘌呤或嘧啶碱基； R1是OH、H、OR3、N3、CN、卤素、CF3、较低的烷基、氨基、较低的烷基氨基、二(较低)烷基氨基或烷氧基； R2是H、磷酸酯或稳定的磷酸酯前药；酰基，或其他药学上可接受的离去基，如苄基、脂质、氨基酸、肽或胆固醇； R3是酰基、烷基、磷酸酯或其他药学上可接受的离去基；或其药学上可接受的盐。
• Synthesis and Antiviral Evaluation of the β-L-Enantiomers of Some Thymine 3′-Deoxypentofuranonucleoside Derivatives
  作者：Christophe Mathé、Gilles Gosselin

  DOI：10.1080/15257770008045443

  日期：2000.10

  3'-Deoxy-beta -L-erythro- (3), 3'-deoxy-beta -L-threo- (6), 2'-fluoro- (7) and 2'-azido-2',3'-dideoxy-beta -L-elythro- (10) pentofuranonucleoside derivatives of thymine have been synthesized and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of thymine with a suitable peracylated 3-deoxy-L-elythro-pentofuranose sugar (1), followed by appropriate chemical modifications. The prepared compounds were tested for their activity against HIV, but they did not show an antiviral effect.
• A Completely Diastereoselective Electrophilic Fluorination of a Chiral, Noncarbohydrate Sugar Ring Precursor:  Application to the Synthesis of Several Novel 2‘-Fluoronucleosides
  作者：J. Jeffrey McAtee、Raymond F. Schinazi、Dennis C. Liotta

  DOI：10.1021/jo9717898

  日期：1998.4.1

  A new and completely diastereoselective method for the introduction of fluorine into a noncarbohydrate sugar ring precursor has been developed. The use of N-fluorodibenzenesulfonimide (5) for the electrophilic fluorination of chiral lactone 4, which is derived from L-glutamic acid, yields the key intermediate 6. This is transformed into an anomeric acetate 8 and is used for the synthesis of a number of novel alpha-2'-fluoronucleosides. Since glutamic acid is used as the synthetic starting material, the L enantiomer may also be synthesized simply by using D-glutamic acid. The incorporation of fluorine into the 2' position of the nucleoside provides several advantages including acid stability of the anomeric bond and general resistance to oxidative metabolism. Further, fluorine is a close mimic of hydroxyl groups in size and polarity and in its ability to act as a hydrogen bond acceptor. This may aid in the recognition of these nucleosides by the enzymes involved in nucleoside activation.