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Towards stereoselective radiosynthesis of α‐[ 11 C]methyl‐substituted aromatic α‐amino acids – a challenge of creation of quaternary asymmetric centre in a very short time
Author(s) -
Popkov Alexander,
Nádvorník Milan,
Kružberská Pavla,
Lyčka Antonín,
Lehel Szabolcs,
Gillings Nicholas
Publication year - 2007
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1268
Subject(s) - chemistry , diastereomer , amino acid , hydrolysis , radiosynthesis , enantiomer , yield (engineering) , synthon , high performance liquid chromatography , organic chemistry , chromatography , stereochemistry , biochemistry , materials science , microbiology and biotechnology , in vivo , metallurgy , biology
Abstract In positron emission tomography (PET) α ‐methyl amino acids have two potential applications: As analogues of neutransmitter precursors for the study of neurodegenerative diseases; as non‐metabolised analogues of proteinogenic amino acids for the study of amino acid uptake into normal and cancer cells. Clinical applications of such amino acids are strongly limited due to their poor availability. We carried out [ 11 C]methylation of metalocomplex synthons derived from protected DOPA or tyrosine. For [ 11 C]methylation, sodium hydroxide (5 mg of fine dry powder) was sealed in a vial, which was flushed with dry nitrogen before addition of a solution of the complex (10 mg) and 11 CH 3 I in 1,3‐dimethylimidazolidin‐2‐one (300 µl). After 10 min at 25°C, a 9% radiochemical yield (decay‐corrected) of a mixture of the diastereomeric α ‐[ 11 C]methylDOPA complexes or a 7% radiochemical yield of a mixture of the diastereomeric α ‐[ 11 C]methyltyrosine complexes was achieved. Individual diastereomers were successfully separated by preparative HPLC, diluted with excess of water and extracted on C18 cartridges. Optimisation of the procedure including hydrolysis of the complexes (hydrolytic deprotection of enantiomerically pure amino acids) and subsequent purification of the enantiomers of α ‐[ 11 C]methylDOPA and α ‐[ 11 C]methyltyrosine is underway. Copyright © 2007 John Wiley & Sons, Ltd.