The labeling of unsaturated γ-hydroxybutyric acid by heavy isotopes of hydrogen: iridium complex-mediated H/D exchange by C─H bond activation vs reduction by boro-deuterides/tritides
| Autor: | Tomáš Elbert, Bente Frølund, Stine B. Vogensen, Aleš Marek, Martin Holst Friborg Pedersen, Rasmus P. Clausen |
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| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
Ketone Hydrogen 010405 organic chemistry Organic Chemistry chemistry.chemical_element 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences Analytical Chemistry BORO Catalysis chemistry.chemical_compound chemistry Deuterium Drug Discovery Radiology Nuclear Medicine and imaging Hydrogen–deuterium exchange Iridium Spectroscopy Phosphine Nuclear chemistry |
| Zdroj: | Journal of Labelled Compounds and Radiopharmaceuticals. 59:476-483 |
| ISSN: | 0362-4803 |
| DOI: | 10.1002/jlcr.3432 |
| Popis: | 3-Hydroxycyclopent-1-ene-1-carboxylic acid (HOCPCA (1)) is a potent ligand for high-affinity γ-hydroxybutyric acid binding sites in the central nervous system. Various approaches to the introduction of a hydrogen label onto the HOCPCA skeleton are reported. The outcomes of the feasible C─H activation of olefin carbon (C-2) by iridium catalyst are compared with the reduction of the carbonyl group (C-3) by freshly prepared borodeuterides. The most efficient iridium catalysts proved to be Kerr bulky phosphine N-heterocyclic species providing outstanding deuterium enrichment (up to 91%) in a short period of time. The highest deuterium enrichment (>99%) was achieved through the reduction of ketone precursor 2 by lithium trimethoxyborodeuteride. Hence, analogical conditions were used for the tritiation experiment. [3 H]-HOCPCA selectively labeled on the position C-3 was synthetized with radiochemical purity >99%, an isolated yield of 637 mCi and specific activity = 28.9 Ci/mmol. |
| Databáze: | OpenAIRE |
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