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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
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  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)
Grant/Contract Number:
SC0012704
OSTI ID:
1473635
Report Number(s):
BNL-209073-2018-JAAM
Journal Information:
Chemistry - A European Journal, Vol. 24, Issue 26; ISSN 0947-6539
Publisher:
ChemPubSoc EuropeCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 4 works
Citation information provided by
Web of Science

References (39)

Application of Serine- and Threonine-Derived Cyclic Sulfamidates for the Preparation of S -Linked Glycosyl Amino Acids in Solution- and Solid-Phase Peptide Synthesis journal March 2002
Synthesis of 11 C, 18 F, 15 O, and 13 N Radiolabels for Positron Emission Tomography journal November 2008
An efficient and practical synthesis of [2- 11 C]indole via superfast nucleophilic [ 11 C]cyanation and RANEY® Nickel catalyzed reductive cyclization journal January 2015
Synthesis of N - t -Boc-L- a -aminoadipic Acid 1- t -Butyl 6-Ethyl Ester from L-Aspartic Acid: A New Route to L-a-Aminoadipic Acid journal January 1982
Synthesis of optically pure .alpha.-amino acids via salts of .alpha.-amino-.beta.-propiolactone journal March 1988
Molecular Imaging with PET journal May 2008
Radiosynthesis of 3-indolyl[1-11C]acetic acid for phyto-PET-imaging: An improved production procedure and formulation method journal September 2014
Investigation of SN2 [11C]cyanation for base-sensitive substrates: an improved radiosynthesis of l-[5-11C]-glutamine journal December 2014
Synthesis of [4-11C]amino acids via ring-opening of aziridine-2-carboxylates journal January 2001
Synthesis of the phytohormone [11C]methyl jasmonate via methylation on a C18 Sep Pak? cartridge
  • Herth, Matthias M.; Thorpe, Michael R.; Ferrieri, Richard A.
  • Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 48, Issue 5 https://doi.org/10.1002/jlcr.933
journal January 2005
Facile synthesis of N-Fmoc-serine-S-GlcNAc: a potential molecular probe for the functional study of O-GlcNAc journal June 2000
A Short and Efficient Synthesis of Neodysiherbaine A by Using Catalytic Oxidative Cyclization journal June 2011
Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(β-11C) DOPA and PET journal September 1999
Radiosynthesis of C-11 labeled auxin (3-indolyl[1-11C]acetic acid) and its derivatives from gramine journal June 2011
Working against Time:  Rapid Radiotracer Synthesis and Imaging the Human Brain journal April 1997
Use of (S)-N-tert-butoxycarbonylaziridine-2-carboxylate derivatives for α-amino acid synthesis journal May 1996
Rapid radiosynthesis of [11C] and [14C]azelaic, suberic, and sebacic acids for in vivo mechanistic studies of systemic acquired resistance in plants journal November 2011
Stereoselective Synthesis of Stable Isotope Labeled L-α-Amino Acids: Synthesis of L−[4−13C] and L−[3,4−13C2]Aspartic Acid journal February 1992
Positron emission tomography (PET) of radiotracer uptake and distribution in living plants: methodological aspects journal December 2012
Fluoride-induced formation and ring opening of cyclic sulfamates from hydroxy triflamides. Synthetic and mechanistic studies journal December 1987
Cyclic sulphamidates: New synthetic precursors for β-functionalised α-amino acids. journal January 1990
Synthesis of no-carrier-added C-11 labeled D- and L-enantiomers of phenylalanine and tyrosine for comparative PET Studies journal January 2003
Preparation and Characterization of L-[5-11C]-Glutamine for Metabolic Imaging of Tumors journal December 2011
Enantioselective synthesis of carbon-11 labeled l-alanine using phase transfer catalysis of Schiff bases journal October 2016
PET in the Diagnosis of Neuroendocrine Tumors journal April 2004
A Short and Efficient Synthesis of Neodysiherbaine A by Using Catalytic Oxidative Cyclization journal June 2011
Synthese von 11 C-, 18 F-, 15 O- und 13 N-Radiotracern für die Positronenemissionstomographie journal November 2008
Application of positron emission tomography and 2-[18F]fluoro-2-deoxy-d-glucose for visualization and quantification of solute transport in plant tissues journal January 2014
Nucleophilic substitution at cyclic sulphamates—routes to NCA [18F]fluoro-analogues of MK 801 journal January 1989
Tetraethylene glycol promoted two-step, one-pot rapid synthesis of indole-3-[1-11C]acetic acid journal January 2015
11C-imaging: methyl jasmonate moves in both phloem and xylem, promotes transport of jasmonate, and of photoassimilate even after proton transport is decoupled journal March 2007
Nuclear physics detector technology applied to plant biology research
  • Weisenberger, A. G.; Kross, B.; Lee, S. J.
  • Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 718 https://doi.org/10.1016/j.nima.2012.08.097
journal August 2013
The synthesis of pyrimidin-4-yl substituted α-amino acids. A versatile approach from alkynyl ketones journal January 1999
Chirospecific synthesis of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane, precursor for carbocyclic nucleoside synthesis. Dieckmann cyclization with an .alpha.-amino acid journal April 1993
Synthesis of l-2,4-Diamino[4-11C]butyric acid and its use in some In vitro and In vivo tumour models journal August 1997
Methods for 11 C- and 18 F-labelling of amino acids and derivatives for positron emission tomography imaging journal March 2013
Radiolabeled Amino Acids for Tumor Imaging with PET:  Radiosynthesis and Biological Evaluation of 2-Amino-3-[ 18 F]fluoro-2-methylpropanoic Acid and 3-[ 18 F]Fluoro-2-methyl-2-(methylamino)propanoic Acid journal May 2002
Facile and Highly Selective Conversion of Nitriles to Amides via Indirect Acid-Catalyzed Hydration Using TFA or AcOH−H 2 SO 4 journal March 2005
Facile and Highly Selective Conversion of Nitriles to Amides via Indirect Acid-Catalyzed Hydration Using TFA or AcOH—H2SO4. journal July 2005

Linked Research (1)

Figures / Tables (15)

Figure 1(p. 6)figure Figure 1
Scheme 1(p. 8)figure Scheme 1
Scheme 2(p. 8)figure Scheme 2
Figure 2(p. 9)figure Figure 2
Figure 3 (A)(p. 10)figure Figure 3 (A)
Figure 3 (B)(p. 11)figure Figure 3 (B)
Scheme 3(p. 12)figure Scheme 3
Figure 4(p. 13)figure Figure 4
Scheme 4(p. 13)figure Scheme 4
Table 1 (A)(p. 14)table Table 1 (A)
Figure 5(p. 15)figure Figure 5
Table 1 (B)(p. 15)table Table 1 (B)
Table 2(p. 16)table Table 2
Table 3(p. 17)table Table 3
Scheme 5(p. 18)figure Scheme 5

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