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

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• 作者：Aleš Marek ; Martin H.F. Pedersen ; Stine B. Vogensen ; Rasmus P. Clausen ; Bente Frø ; lund and Tomá ; š Elbert
• 刊名：Journal of Labelled Compounds and Radiopharmaceuticals
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：59
• 期：12
• 页码：476-483
• 全文大小：705K
• ISSN：1099-1344

文摘

3-Hydroxycyclopent-1-ene-1-carboxylic acid (HOCPCA (<b>1b>)) 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 <b>2b> by lithium trimethoxyborodeuteride. Hence, analogical conditions were used for the tritiation experiment. [³H]-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.