The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains a challenge. This is especially true for the synthesis of carbon‐11‐labeled AAs given the short half‐life of carbon‐11 (¹¹C, t_1/2=20.4 min). A facile synthetic pathway to prepare enantiomerically pure ¹¹C‐labeled l‐asparagine was developed using a partially protected serine as a starting material with a four‐step transformation providing a chiral five‐membered cyclic sulfamidate as the radiolabeling precursor. Its structure and absolute configuration were confirmed by X‐ray crystallography. Utilizing a [¹¹C]cyanide nucleophilic ring opening reaction followed by selective acidic hydrolysis and deprotection, enantiomerically pure l‐[4‐¹¹C]asparagine was synthesized. Further optimization of reaction parameters, including base, metal ion source, solvent, acid component, reaction temperature and reaction time, a reliable two‐step method for synthesizing l‐[4‐¹¹C]asparagine was presented: within a 45±3 min (n=5, from end‐of‐bombardment), the desired enantiomerically pure product was synthesized with the initial nucleophilic cyanation yield of 69±4 % (n=5) and overall two‐step radiochemical yield of 53±2 % (n=5) based on starting [¹¹C]HCN, and with radiochemical purity of 96±2 % (n=5).

中文翻译：

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手性环状氨基磺酸酯前体的开环亲核11C氰化反应合成l [[4-11C]天冬酰胺

合成方便的，快速的方法以合成放射性标记的，对映体纯的氨基酸（AAs）作为潜在的正电子发射断层扫描（PET）成像剂，以绘制活体生物的各种生化转变仍然是一个挑战。鉴于碳11的半衰期较短（¹¹ C，t _1/2 = 20.4分钟），对于碳11标记的AA的合成尤其如此。制备对映体纯的¹¹ C标记的l的简便合成途径用部分保护的丝氨酸为原料开发了天冬酰胺，并进行了四步转化，提供了手性五元环氨基磺酸盐作为放射性标记前体。X射线晶体学证实了其结构和绝对构型。利用[ ¹¹ C]的氰化物亲核开环反应，接着通过选择性酸性水解和脱保护，对映体纯升- [4- ¹¹ C]天冬酰胺的合成。反应参数的进一步优化，包括碱金属离子源，溶剂，酸成分，反应温度和反应时间，用于合成可靠两步法升- [4- ¹¹ C]天冬酰胺被提出：45±3分钟内（n从轰击结束= 5，合成了所需的对映体纯产物，其初始亲核氰化产率为69±4％（n = 5），两步放射化学总产率为53±2％（n = 5） ）为起始原料[ ¹¹ C] HCN，放射化学纯度为96±2％（n = 5）。