The labeling of unsaturated gamma-hydroxybutyric acid by heavy isotopes of hydrogen: iridium complex-mediated H/D exchange by C-H bond activation vs reduction by boro-deuterides/tritides

0467405 - ÚOCHB 2017 RIV GB eng J - Journal Article
Marek, Aleš - Pedersen, M. H. F. - Vogensen, S. B. - Clausen, R. P. - Frolund, B. - Elbert, Tomáš
The labeling of unsaturated gamma-hydroxybutyric acid by heavy isotopes of hydrogen: iridium complex-mediated H/D exchange by C-H bond activation vs reduction by boro-deuterides/tritides.
Journal of Labelled Compounds and Radiopharmaceuticals. Roč. 59, č. 12 (2016), s. 476-483. ISSN 0362-4803. E-ISSN 1099-1344
Institutional support: RVO:61388963
Keywords : C-H activation * borotritides * hydrogen/deuterium exchange * iridium catalyst * tritium-labeled gamma-hydroxybutyric acid
Subject RIV: CC - Organic Chemistry
Impact factor: 1.745, year: 2016

3-Hydroxycyclopent-1-ene-1-carboxylic acid (HOCPCA (1)) is a potent ligand for high-affinity gamma-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. [H-3]-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.
Permanent Link: http://hdl.handle.net/11104/0265508