1-(2,3-dideoxy-2-fluoro-β-D-erythro-pentofuranosyl)thymine | 121353-93-3

• 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-2-fluoro-β-D-erythro-pentofuranosyl)thymine
• 英文别名: 1-<2-fluoro-2,3-dideoxy-β-D-erythro-pentofuranosyl>thymine；1-<2,3-dideoxy-2-fluoro-β-D-erythro-pentafuranosyl>thymine；1(2'-fluoro-2',3'-dideoxy-β-D-erythro-pentofuranosyl)thymine；1-[(2R,3R,5S)-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 121353-93-3
• 化学式: C₁₀H₁₃FN₂O₄
• 分子量: 244.223
• InChiKey: NPHYUIHLLMXOFR-LKEWCRSYSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Predicted)

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：

  2,2'-anhydro-1-(5-O-trityl-β-D-arabinofuranosyl)thymine 在 sodium hydroxide 、 偶氮二异丁腈 、 三正丁基氢锡 、 溶剂黄146 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 13.0h， 生成 1-(2,3-dideoxy-2-fluoro-β-D-erythro-pentofuranosyl)thymine
  参考文献：
  名称：

  潜在的抗HIV-1核苷的氟化糖类似物。

  摘要：

  为了获得具有优于AZT，FLT或D4T的治疗指数的药物，合成了抗HIV-1核苷的几种类似物。这些包括2'，3'-dideoxy-2'，3'-difluoro-5-methyluridine（13），其阿拉伯糖类似物19，arab-5--5-甲基胞嘧啶类似物21、3'-脱氧2'，3'-二氢-2'-氟胸苷（25），3'-叠氮基2'，3'-二脱氧基2'-氟-5-甲基尿苷（29），2'-叠氮基3'-氟-2'，3'-双脱氧-5-甲基尿苷（31）和2'3'-二脱氧-2'-氟-5-甲基尿苷（37）。对这些新核苷在体外针对HIV和猫TLV的活性进行了筛选。没有一种化合物显示出明显的活性。有趣的是，活性抗HIV核苷的糖部分有这么小的修饰（即

  DOI：

  10.1021/jm00109a017

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 of 2-Fluoro Sugar and Its Condensation Reaction with Silylated Thymine
  作者：Shigeo Niihata、Takashi Ebata、Hiroshi Kawakami、Hajime Matsushita

  DOI：10.1246/bcsj.68.1509

  日期：1995.5

  2,3-Dideoxy-2-fluoro-D-erythro-pentofuranose was easily prepared from 3-DPA lactone. The condensation reaction between 1-O-acetyl derivative of this sugar and silylated thymine in the presence of TMSOTf proceeded in a poorly stereoselective manner.

  2,3-Dideoxy-2-fluoro-D-erythro-pentofuranose 很容易从 3-DPA 内酯制备。在 TMSOTf 存在下，该糖的 1-O-乙酰基衍生物与甲硅烷基化胸腺嘧啶之间的缩合反应以较差的立体选择性方式进行。
• 3'-Fluoro-2',3'-dideoxy-5-chlorouridine: most selective anti-HIV-1 agent among a series of new 2'- and 3'-fluorinated 2',3'-dideoxynucleoside analogs
  作者：Arthur Van Aerschot、Piet Herdewijn、Jan Balzarini、Rudi Pauwels、Erik De Clercq

  DOI：10.1021/jm00128a013

  日期：1989.8

  A series of 2'- and 3'-fluorinated 2',3'-dideoxynucleosides and 3'-azido-2',3'-dideoxynucleosides were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus-1 (HIV-1) replication in MT-4 cells. Neither conversion of 3'-fluoro- or 3'-azido-2',3'-dideoxyadenosine to the corresponding inosine derivatives nor 8-bromination of 2',3'-dideoxyadenosine resulted in increased

  合成了一系列的2'-和3'-氟化2'，3'-双脱氧核苷和3'-叠氮基2'，3'-双脱氧核苷，并评估了其对人免疫缺陷病毒1（HIV-1）的抑制活性在MT-4细胞中复制。将3'-氟-或3'-叠氮基-2'，3'-二脱氧腺苷转化为相应的肌苷或将2'，3'-二脱氧腺苷进行8-溴化都不会增加抗HIV-1的活性。在赤型或苏型构型中引入2'-氟也没有导致母体2'，3'-二脱氧核苷的抗HIV-1活性提高。1-（2-氟-2,3-二脱氧-β-D-苏-戊呋喃糖基）胞嘧啶和1-（2-氟-2,3-二脱氧-β-D-四氢呋喃呋喃糖基）胸腺嘧啶仅具有少量活性。但是，3'-fluoro-2'，3' -dideoxyuridine（FddUrd）被证明是有效的且是相对无毒的HIV-1抑制剂。尝试制备FddUrd的5-卤代衍生物，以进一步提高其抗HIV效能和选择性。在这些5-卤代衍生物中，3'-氟-2'，3'-二脱氧-5-氯尿苷
• 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.
• 2'-FLUOROFURANOSYL DERIVATIVES AND NOVEL METHOD OF PREPARING 2'-FLUOROPYRIMIDINE AND 2'-FLUOROPURINE NUCLEOSIDES
  申请人：THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce

  公开号：EP0540686B1

  公开（公告）日：1995-08-30