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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

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 as 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 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 startingmore » [ 11C]HCN, and with radiochemical purity of 96 ± 2% (n = 5).« less

Authors:
 [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
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1473635
Report Number(s):
BNL-209073-2018-JAAM
Journal ID: ISSN 0947-6539
Grant/Contract Number:  
SC0012704
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Chemistry - A European Journal
Additional Journal Information:
Journal Volume: 24; Journal Issue: 26; Journal ID: ISSN 0947-6539
Publisher:
ChemPubSoc Europe
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Xu, Youwen, Cankaya, Aylin Sibel, Hoque, Ruma, Lee, So Jeong, Shea, Colleen, Kersting, Lena, Schueller, Michael, Fowler, Joanna S., Szalda, David, Alexoff, David, Riehl, Barbara, Gleede, Tassilo, Ferrieri, Richard A., and Qu, Wenchao. Synthesis of l -[4- 11 C]Asparagine by Ring-Opening Nucleophilic 11 C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor. United States: N. p., 2018. Web. doi:10.1002/chem.201801029.
Xu, Youwen, Cankaya, Aylin Sibel, Hoque, Ruma, Lee, So Jeong, Shea, Colleen, Kersting, Lena, Schueller, Michael, Fowler, Joanna S., Szalda, David, Alexoff, David, Riehl, Barbara, Gleede, Tassilo, Ferrieri, Richard A., & Qu, Wenchao. Synthesis of l -[4- 11 C]Asparagine by Ring-Opening Nucleophilic 11 C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor. United States. doi:10.1002/chem.201801029.
Xu, Youwen, Cankaya, Aylin Sibel, Hoque, Ruma, Lee, So Jeong, Shea, Colleen, Kersting, Lena, Schueller, Michael, Fowler, Joanna S., Szalda, David, Alexoff, David, Riehl, Barbara, Gleede, Tassilo, Ferrieri, Richard A., and Qu, Wenchao. Mon . "Synthesis of l -[4- 11 C]Asparagine by Ring-Opening Nucleophilic 11 C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor". United States. doi:10.1002/chem.201801029.
@article{osti_1473635,
title = {Synthesis of l -[4- 11 C]Asparagine by Ring-Opening Nucleophilic 11 C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor},
author = {Xu, Youwen and Cankaya, Aylin Sibel and Hoque, Ruma and Lee, So Jeong and Shea, Colleen and Kersting, Lena and Schueller, Michael and Fowler, Joanna S. and Szalda, David and Alexoff, David and Riehl, Barbara and Gleede, Tassilo and Ferrieri, Richard A. and Qu, Wenchao},
abstractNote = {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).},
doi = {10.1002/chem.201801029},
journal = {Chemistry - A European Journal},
number = 26,
volume = 24,
place = {United States},
year = {Mon Mar 05 00:00:00 EST 2018},
month = {Mon Mar 05 00:00:00 EST 2018}
}

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