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

Journal Article · · Chemistry - A European Journal
 [1];  [2];  [3];  [3];  [1];  [2];  [1];  [3];  [4];  [1];  [2];  [2];  [1]; ORCiD logo [1]
  1. Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States); Johannes Gutenberg Univ., Mainz (Germany)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., NY (United States)
  4. City Univ. (CUNY), NY (United States). Buruch College
+ Show Author Affiliations

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 as 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 fivemembered 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).

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Grant/Contract Number:
SC0012704
OSTI ID:
1473635
Report Number(s):
BNL--209073-2018-JAAM
Journal Information:
Chemistry - A European Journal, Journal Name: Chemistry - A European Journal Journal Issue: 26 Vol. 24; ISSN 0947-6539
Publisher:
ChemPubSoc EuropeCopyright Statement
Country of Publication:
United States
Language:
English

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