Synthesis of Optically Pure 4-Fluoro-Glutamines as Potential Metabolic Imaging Agents for Tumors
Synthesis of Optically Pure 4-Fluoro-Glutamines as Potential Metabolic Imaging Agents for Tumors
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DOI：
10.1021/ja109203d
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发表时间：
2011-02-02
影响因子：
15
通讯作者：
Kung, Hank F.
中科院分区：
文献类型：
--
作者：
Qu, Wenchao;Zha, Zhihao;Kung, Hank F.
利用Passerini三组分反应，建立了制备四种立体异构体4-氟谷氨酰胺的通用合成路线。高效构建了4-取代谷氨酰胺衍生物骨架。随后的四步反应，以“中和”TASF氟化为重点，提供了高产量和优异光学纯度的所需产品。采用18-冠-6/KHCO3或K[222]/K2CO3催化体系，成功制备了光学纯的氟-18标记的4-氟脲胺。利用9L肿瘤细胞和SF188（Bcl-xL）肿瘤细胞（一种来源于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）结合使用谷氨酰胺作为替代能源进行肿瘤体内成像提供了强有力的证据。
A versatile synthetic 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 4-fluoroglutamines were also successfully prepared using either a 18-crown-6/KHCO3 or K[222]/K2CO3 catalysis system. Preliminary cell uptake and inhibition studies using the 9L tumor cells and SF188(Bcl-xL) tumor cells (a glutamine addicted tumor derived from glioblastoma) provided strong evidence for their potential application in conjunction with positron emission tomography (PET) for in vivo imaging of tumors, which use glutamine as an alternative energy source.