Synthesis of l-[4-11C]Asparagine by Ring-Opening Nucleophilic 11C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor

Youwen Xu, Aylin Sibel Cankaya, Ruma Hoque, So Jeong Lee, Colleen Shea, Lena Kersting, Michael Schueller, Joanna S. Fowler, David Szalda, David Alexoff, Barbara Riehl, Tassilo Gleede, Richard A. Ferrieri, Wenchao Qu

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5 Scopus citations

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).

Original languageEnglish
Pages (from-to)6848-6853
Number of pages6
JournalChemistry - A European Journal
Volume24
Issue number26
DOIs
StatePublished - 7 May 2018
Externally publishedYes

Keywords

  • amino acids
  • nucleophilic
  • radiochemistry
  • ring opening
  • sulfamidate

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