(2S,4R)‐4‐[¹⁸F]fluoroglutamine | 1262523-93-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4R)‐4‐[¹⁸F]fluoroglutamine
• 英文别名: [¹⁸F]FGln；(2S,4S)-2,5-diamino-4-(18F)fluoranyl-5-oxopentanoic acid
• CAS: 1262523-93-2
• 化学式: C₅H₉FN₂O₃
• 分子量: 163.138
• InChiKey: PGEYFCBAWGQSGT-DIXDPKRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2S,4S)-tert-butyl 2-(tert-butoxycarbonylamino)-5-oxo-4-(tosyloxy)-5-(2,4,6-trimethoxybenzylamino)pentanoate 在 potassium carbonate 、 苯甲醚 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 0.41h， 生成 (2S,4R)‐4‐[¹⁸F]fluoroglutamine
  参考文献：
  名称：

  [EN] SINGLE DIASTEREOMERS OF 4-FLUOROGLUTAMINE AND METHODS FO THEIR PREPARATION AND USE
  [FR] DIASTÉRÉOMÈRES UNIQUES DE 4-FLUOROGLUTAMINE ET PROCÉDÉS POUR LEUR PRÉPARATION ET LEUR UTILISATION

  摘要：

  本发明涉及具有至少80%对映异构体过量的4-氟谷氨酸的单一对映异构体。还描述了制备单一对映异构体的方法，以及使用放射标记的4-氟谷氨酸的单一对映异构体作为成像剂的方法。

  公开号：

  WO2011020018A1

文献信息

• Synthesis of Optically Pure 4-Fluoro-Glutamines as Potential Metabolic Imaging Agents for Tumors
  作者：Wenchao Qu、Zhihao Zha、Karl Ploessl、Brian P. Lieberman、Lin Zhu、David R. Wise、Craig B. Thompson、Hank F. Kung

  DOI：10.1021/ja109203d

  日期：2011.2.2

  route to prepare all four stereoisomeric 4-fluoro-glutamines was developed by exploiting a Passerini three-component reaction. The skeleton of 4-substituted glutamine derivatives was efficiently constructed. Subsequent four-step reactions, highlighted by a "neutralized" TASF fluorination, provided the desired products with high yields and excellent optical purity. The optically pure fluorine-18 labeled

  通过利用 Passerini 三组分反应开发了一种用于制备所有四种立体异构 4-氟-谷氨酰胺的通用合成路线。有效构建了 4-取代谷氨酰胺衍生物的骨架。随后的四步反应，以“中和”的 TASF 氟化为重点，提供了具有高产率和优异光学纯度的所需产物。使用 18-crown-6/KHCO(3) 或 K[222]/K(2)CO(3) 催化系统也成功地制备了光学纯氟 18 标记的 4-氟谷氨酰胺。使用 9L 肿瘤细胞和 SF188(Bcl-xL) 肿瘤细胞（一种源自胶质母细胞瘤的谷氨酰胺成瘾肿瘤）进行的初步细胞摄取和抑制研究为它们与正电子发射断层扫描 (PET) 结合用于体内成像的潜在应用提供了强有力的证据。肿瘤，
• Initial experience in synthesis of (2S,4R)‐4‐[18F]fluoroglutamine for clinical application
  作者：Yan Zhang、Lifang Zhang、Jianhua Yang、Zehui Wu、Karl Ploessl、Zhihao Zha、Fei Liu、Xiaoxia Xu、Hua Zhu、Zhi Yang、Lin Zhu、Hank F. Kung

  DOI：10.1002/jlcr.3719

  日期：2019.5.15

  We report initial experience in synthesis of (2S,4R)‐4‐[18F]fluoroglutamine, [18F]FGln, which has been used as a tool for monitoring glutamine metabolism in cancer patients. [18F]FGln was prepared by a fully automated PET‐MF‐2V‐IT‐I synthesizer under GMP‐compliant conditions for routine clinical studies. The total radiosynthesis time was about 65 minutes, the decay‐corrected radiochemical yield was 18.0 ± 4.2% (n = 59; failure n = 15), and the radiochemical purity was greater than 90%. In some situations, the yields were low (less than 5%), and the most likely cause of this problem is the initial fluorination step; the fluoride ion might not have been fully activated. In other occasions, low final radiochemical purity was often associated with the failure of the second step—removal of protection groups by anhydrous trifluoroacetic acid. A trace amount of water led to production of undesired 4‐[18F]fluoroglutamic acid. Knowledge learned from the successes and failures of synthesis may be helpful to identify critical steps and pitfalls for preparation of this clinically useful metabolic probe, [18F]FGln, for imaging glutamine utilization in tumor of cancer patients.