2'-deoxy-2'-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil | 241144-93-4

• 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-2'-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil
• 英文别名: 1-[(2R,3S,4R,5R)-3-(18F)fluoranyl-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 241144-93-4
• 化学式: C₁₀H₁₃FN₂O₅
• 分子量: 259.224
• InChiKey: GBBJCSTXCAQSSJ-MSYRQUNGSA-N

物化性质

• 密度：
  1.559±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  18
• 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：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-O-(trifluoromethylsulfonyl)-1,3,5-tri-O-benzoyl-α-D-ribofuranose 在 [18F]-tetrabutylammonium fluoride 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 六甲基二硅氮烷 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 2'-deoxy-2'-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil
  参考文献：
  名称：

  [EN] [18F] FMAU LABELING FOR PET IMAGING OF CANCER PATIENTS
  [FR] MARQUAGE DE FMAU AU [18F] POUR IMAGERIE TEP DE PATIENTS ATTEINTS D'UN CANCER

  摘要：

  本文提供一种符合CGMP标准的方法和标签套件，用于在一锅反应中合成2'-脱氧-2'-[18F]氟-5-甲基-1-beta-D-阿拉伯核糖基尿嘧啶。还披露了可以在自动合成系统中组装的标签套件，以实现此反应。

  公开号：

  WO2019191642A1

文献信息

• A novel method for stereospecific fluorination at the 2′-arabino-position of pyrimidine nucleoside: synthesis of [18F]-FMAU
  作者：Nashaat Turkman、Juri G. Gelovani、Mian M. Alauddin

  DOI：10.1002/jlcr.1797

  日期：2010.11

  produced the desired [18F]FMAU. The average radiochemical yield was 2.0% (decay corrected, n=6), from the end of bombardment. Radiochemical purity was >99%, and specific activity was >1800 mCi/µmol. Synthesis time was 95–100 min from the end of bombardment. This direct fluorination is a novel method for synthesis of [18F]FMAU, and the method should be suitable for production of other 5-substituted pyrimidine

  嘧啶核苷在 2'-阿拉伯位置的直接氟化被认为是极其困难的，如果不是不可能的话。2'-deoxy-2'-fluoro-5-methy-1-β-D-arabinofuranosyluracil (FMAU) 及其 5-取代类似物的常规合成涉及 1,3,5-tri-O-苯甲酰基的立体定向氟化-α-D-呋喃核糖-2-磺酸酯，然后在 C1 位进行溴化，然后与嘧啶-双-三甲基甲硅烷基醚偶联。根据这种方法开发了几种放射性标记的核苷类似物，包括 [ 18 F] FMAU 和其他 5 取代的类似物。然而，使用这种多步骤方法常规生产这些化合物是不方便的并且限制了它们的临床应用。我们开发了一种新的前体和方法，用于在 2'-阿拉伯位置直接氟化预先形成的核苷类似物，通过[18F]FMAU的放射合成举例说明。2'-methylsulfonyl-3',5'-O-tetrahydropyranyl-N3-Boc-5-me
• A general synthesis of 2?-deoxy-2?-[18F]fluoro-1-?-D-arabinofuranosyluracil and its 5-substituted nucleosides
  作者：Mian M. Alauddin、Peter S. Conti、John D. Fissekis

  DOI：10.1002/jlcr.637

  日期：2003.3.30

  Several 2′-deoxy-2′-[18F]fluoro-1-β-D-arabinofuranosyluracil derivatives have been synthesized. Coupling of 1-bromo-2-deoxy-2-[18F]fluoro-3,5-di-O-benzoyl-α-D-arabinofuranose 2 with protected uracil derivatives 3a–e followed by hydrolysis and high-performance liquid chromatography purification produced the radiolabeled nucleosides 4a–e in 15–30% yield (d. c.), >99% radiochemical purity and 55.5–103.6 GBq/µmol specific activities. Copyright © 2003 John Wiley & Sons, Ltd.

  我们合成了几种 2′-脱氧-2′-[18F]氟-1-β-D-阿拉伯呋喃糖基尿嘧啶衍生物。将 1-溴-2-脱氧-2-[18F]氟-3,5-二-O-苯甲酰基-α-D-阿拉伯呋喃糖 2 与受保护的尿嘧啶衍生物 3a-e 偶联，然后进行水解和高效液相色谱纯化，得到了放射性标记的核苷 4a-e，收率为 15-30% (d.c.)，放射化学纯度大于 99%，比活度为 55.5-103.6 GBq/µmol。Copyright © 2003 John Wiley & Sons, Ltd. All Rights Reserved.
• Synthesis of [18F]-labeled 2?-deoxy-2?-fluoro-5-methyl-1-?-D-arabinofuranosyluracil ([18F]-FMAU)
  作者：Mian M. Alauddin、Peter S. Conti、John D. Fissekis

  DOI：10.1002/jlcr.549

  日期：2002.6

  Synthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU) is reported. 2-Deoxy-2-[18F]fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofuranose 2 was prepared by the reaction of the respective triflate 1 with tetrabutylammonium[18F]fluoride. The fluorosugar 2 was converted to its 1-bromo-derivative 3 and coupled with protected thymine 4. The crude product mixture (5a and 5b) was hydrolyzed in base and purified by HPLC to obtain the radiolabeled FMAU 6a. The radiochemical yield of 6a was 20–30% decay corrected (d.c.) in four steps with an average of 25% in four runs. Radiochemical purity was >99% and average specific activity was 2300 mCi/μmol at the end of synthesis (EOS). The synthesis time was 3.5–4.0 h from the end of bombardment (EOB). Copyright © 2002 John Wiley & Sons, Ltd.

  报道了 2'-脱氧-2'-[18F]氟-5-甲基-1-β-D-阿拉伯呋喃糖尿嘧啶 ([18F]-FMAU) 的合成。 2-脱氧-2-[ 18 F]氟-1,3,5-三-O-苯甲酰基-α-D-阿拉伯呋喃糖2通过相应的三氟甲磺酸酯1与四丁基铵[ 18 F]氟化物的反应制备。将氟糖2转化为其1-溴衍生物3并与受保护的胸腺嘧啶4偶联。将粗产物混合物(5a和5b)在碱中水解并通过HPLC纯化以获得放射性标记的FMAU 6a。 6a 的放射化学产率在四个步骤中衰减校正为 20-30%（d.c.），四次运行的平均值为 25%。放射化学纯度 >99%，合成结束时 (EOS) 平均比活度为 2300 mCi/μmol。合成时间为轰击结束（EOB）后 3.5-4.0 小时。版权所有 © 2002 约翰·威利父子有限公司
• 胸腺嘧啶类化合物及其作为分子探针靶材料的 用途
  申请人：医影生物纳米技术(苏州)有限公司

  公开号：CN101979398B

  公开（公告）日：2016-05-18

  本发明提供下述通式3，3’，5’-保护的2-去氧胸腺嘧啶的化合物和制备方法及其作为肿瘤分子探针的应用。
• A fully automated synthesis of [¹⁸F]-FEAU and [¹⁸F]-FMAU using a novel dual reactor radiosynthesis module
  作者：Vincenzo Paolillo、Stefan Riese、Juri G. Gelovani、Mian M. Alauddin

  DOI：10.1002/jlcr.1674

  日期：2009.11

  2′-Deoxy-2′-[18F]fluoro-5-substituted-1-β-D-arabinofuranosyluracils, including 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil [18F]FMAU and [18F]FEAU are established radiolabeled probes to monitor cellular proliferation and herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression with positron emission tomography. For clinical applications, a fully automated CGMP-compliant radiosynthesis is necessary for production of these probes. However, due to multiple steps in the synthesis, no such automated synthetic protocols have been developed. We report here a fully automated synthesis of [18F]-FEAU and [18F]-FMAU on a prototype dual reactor module TRACERlab FX FN. The synthesis was performed by using a computer-programmed standard operating procedure, and the product was purified on a semipreparative high-performance liquid chromatography (HPLC) integrated with the synthesis module using 12% EtOH in 50 mM Na2HPO4. Finally, the percentage of alcohol was adjusted to 7% by adding Na2HPO4 and filtered through a Millipore filter to make dose for human. The radiochemical yield on the fluorination was 40±10% (n=10), and the overall yields were 4±1% (d. c.), from the end of the bombardment; [18F]FEAU (n=7) and [18F]FMAU (n=3). The radiochemical purity was >99%, specific activity was 1200–1300 mCi/µmol. The synthesis time was 2.5 h. This automated synthesis should be suitable for production of [18F]FIAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and other 5-substitued thymidine analogues. Copyright © 2009 John Wiley & Sons, Ltd.

  2′-脱氧-2′-[18F]氟-5-取代-1-β-D-阿拉伯呋喃糖基尿嘧啶、包括 2′-脱氧-2′-[18F]氟-5-甲基-1-β-D-阿拉伯呋喃糖基尿嘧啶 [18F]FMAU 和 [18F]FEAU 是成熟的放射性标记探针，可通过正电子发射断层扫描监测细胞增殖和单纯疱疹病毒 1 型胸苷激酶（HSV1-tk）报告基因的表达。在临床应用中，生产这些探针需要符合 CGMP 标准的全自动放射合成工艺。然而，由于合成过程中存在多个步骤，目前尚未开发出此类自动合成方案。我们在此报告在双反应器原型模块 TRACERlab FX FN 上全自动合成 [18F]-FEAU 和 [18F]-FMAU 的情况。合成是通过计算机编程的标准操作程序进行的，产物在与合成模块集成的半分离高效液相色谱（HPLC）上用 12% EtOH 在 50 mM Na2HPO4 中进行纯化。最后，通过添加 Na2HPO4 将酒精比例调整为 7%，并通过密理博滤器过滤，以制成人体剂量。从轰击结束算起，[18F]FEAU（n=7）和[18F]FMAU（n=3）的氟化放射化学收率为 40±10%（n=10），总收率为 4±1%（d.c.）。放射性纯度大于 99%，比活度为 1200-1300 mCi/µmol。这种自动合成方法适用于生产[18F]FIAU、[18F]FFAU、[18F]FCAU、[18F]FBAU和其他5-取代胸苷类似物。版权所有 © 2009 John Wiley & Sons, Ltd. 保留所有权利。