β-(D)-N4-acetyl-2’,3’-dideoxy-2’-fluoro-cytidine | 202272-26-2

• 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-(D)-N4-acetyl-2’,3’-dideoxy-2’-fluoro-cytidine
• 英文别名: N-[1-[(2R,3R,5S)-3-fluoro-5-(hydroxymethyl)tetrahydrofuran-2-yl]-2-oxo-pyrimidin-4-yl]acetamide；N-[1-[(2R,3R,5S)-3-fluoro-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]acetamide
• CAS: 202272-26-2
• 化学式: C₁₁H₁₄FN₃O₄
• 分子量: 271.248
• InChiKey: MFABATGYVBMUAJ-QXFUBDJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  91.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  β-(D)-N4-acetyl-2’,3’-dideoxy-2’-fluoro-cytidine 在 氨 作用下， 以 甲醇 为溶剂， 反应 0.08h， 以100%的产率得到β-(D)-2’,3’-Dideoxy-2’-fluoro-cytidine
  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
• 作为产物：
  描述：

  5-(羟基甲基)二氢-2(3H)-呋喃酮 在 4-二甲氨基吡啶 、 氟化铵 、 三氟甲磺酸三甲基硅酯 、 二异丁基氢化铝 、 N-氟代双苯磺酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 β-(D)-N4-acetyl-2’,3’-dideoxy-2’-fluoro-cytidine
  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。
• 2'-fluoronucleosides
  申请人：Emory University

  公开号：EP2392580A1

  公开（公告）日：2011-12-07

  2'-Fluoronucleoside 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 general formulae (I), (II), (III), (IV) wherein Base is a purine or pyrimidine base; R1 is OH, H, OR3, N3, CN, halogen, including F, or CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base; R2 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R2 is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and R3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.

  本发明公开了 2'-氟核苷化合物，可用于治疗乙型肝炎感染、丙型肝炎感染、艾滋病病毒和异常细胞增殖，包括肿瘤和癌症。这些化合物具有通式 (I)、(II)、(III)、(IV)，其中碱基是嘌呤或嘧啶碱基；R1 是 OH、H、OR3、N3、CN、卤素（包括 F）或 CF3、低级烷基、氨基、低级烷基氨基、二（低级）烷基氨基或烷氧基，碱基是指嘌呤或嘧啶碱基；R2 是 H、磷酸盐（包括单磷酸盐、二磷酸盐、三磷酸盐或稳定的磷酸盐原药）、酰基或其他药学上可接受的离去基团，在体内给药时，可提供 R2 是 H 或磷酸盐的化合物；磺酸酯，包括烷基或芳烷基磺酰基（包括甲磺酰基）、苄基（其中苯基可选地被一个或多个如上文芳基定义所述的取代基取代）、脂质、氨基酸、肽或胆固醇；以及 R3 为酰基、烷基、磷酸酯或其他药学上可接受的离去基团，该离去基团在体内给药时可裂解为母体化合物或其药学上可接受的盐。
• 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.