Synthesis of l ‐[4‐11C]Asparagine by Ring‐Opening Nucleophilic 11C‐Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor
Year: 2018
Type: article
Abstract: 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, t1/2=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).
Source: Chemistry - A European Journal
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2790123290