Speaker
Dr
Alexander Popkov
(Department of Information Systems, Faculty of Health and Social Studies, University of South Bohemia)
Description
PET diagnostics using radiolabelled amino acids is an emerging branch of nuclear medicine. This includes visualisation and grading of brain, neuroendocrine and prostata tumours, measurement of protein synthesis rate in tumour cells, quantitative in vivo measurement of dopamine and serotonin metabolism in brain. Development of clinical applications is limited by complexicity of robotic devices necessary for multi-step preparation of the enantiomerically pure amino acids. Robust and reliable approaches not requiring sophisticated separation of radiolabelled intermediates have to be created for everyday clinical routine. Nickel(II) complexes of Schiff bases of (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide (BPB) and α-amino acids were developed as artificial analogues of pyridoxal 5'-phosphate (PLP)-dependent enzymes for asymmetric synthesis of amino acids. Current approach using BPB in nickel(II) complex of its Schiff base with glycine allows easy preparation of O-(2'-[18F]fluoroethyl)-L-tyrosine ([18F]FET) with 94-97% e. e. with no need for separation of diastereomers of alkylated complexes. Preparation of 6-[18F]FDOPA using the same starting nickel complex gives only 77±5% e. e. without separation of diastereomers of alkylated complexes while the same preparation of α-[11C]DOPA leads to 92-99% e. e. Preparation of α-methyl DOPA or α-methyltyrosine labelled with carbon-11 or fluorine-18 requires formation of quaternary chiral centre, stereochemistry of which is controlled kinetically. Kinetic control is much less efficient then thermodynamic one, thus diastereomeric excess of complexes of α-methyl amino acids is inferior. Enhancement of stereodivergent power in both thermodynamically and kinetically controlled alkylation reaction is the biggest priority in development of new metallocomplex tools for the preparation of PET amino acids.
In this presentation the evaluation of new amino acids synthons bearing C2-symmetric benzyl groups with electron-donating and electron-withdrawing substituents will be described. Compatibility of amino acid side chains protective groups will be assessed in relation to the reaction conditions used for preparation of the complexes.
Primary author
Dr
Alexander Popkov
(Department of Information Systems, Faculty of Health and Social Studies, University of South Bohemia)
Co-authors
Prof.
Antonín Lyčka
(Research Institute for Organic Syntheses)
Dr
Jiří Hanusek
(nstitute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice)
Dr
Jiří Čermák
(Research Institute for Organic Syntheses)
Prof.
Michal Holčapek
(Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice)
Dr
Milan Nádvorník
(Department of General and Inorganic Chemistry, Faculty of Chemical Technology , University of Pardubice)
Dr
Robert Jirásko
(Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice)
Dr
Tomáš Weidlich
(Institute of Environmental and Chemical Engineering, Faculty of Chemical Technology , University of Pardubice)
Prof.
Vratislav Langer
(Department of Chemical and Biological Engineering, Division of Materials and Surface Chemistry, Subdivision of Inorganic Environmental Chemistry, Chalmers University of Technology)
