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.
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. [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.
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, v.v.i., Flemingovo nám. 2, Prague 6, 16610, Czech Republic. marek@uochb.cas.cz.|Center for Nuclear Technologies, DTU Nutech/Hevesy Laboratory, Technical University of Denmark, Frederiksborgvej 399, Building 202, Roskilde, 4000, Denmark. marek@uochb.cas.cz.
Aleš
A
Marek
Center for Nuclear Technologies, DTU Nutech/Hevesy Laboratory, Technical University of Denmark, Frederiksborgvej 399, Building 202, Roskilde, 4000, Denmark.
Martin H F
MH
Pedersen
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Stine B
SB
Vogensen
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Rasmus P
RP
Clausen
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Bente
B
Frølund
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, v.v.i., Flemingovo nám. 2, Prague 6, 16610, Czech Republic.
Tomáš
T
Elbert
D000475:Alkenes / Q000737:chemistry; D001895:Boron / Q000737:chemistry*; D002384:Catalysis; D003903:Deuterium / Q000737:chemistry*; D041961:Deuterium Exchange Measurement; D006885:Hydroxybutyrates / Q000737:chemistry*; D007495:Iridium / Q000737:chemistry*; D007553:Isotope Labeling; D008024:Ligands; D010084:Oxidation-Reduction; D014316:Tritium / Q000737:chemistry*
D000475:Alkenes; D006885:Hydroxybutyrates; D008024:Ligands; D014316:Tritium; C111420:4-hydroxybutyric acid; D007495:Iridium; D003903:Deuterium; D001895:Boron
C─H activation; borotritides; hydrogen/deuterium exchange; iridium catalyst; tritium-labeled γ-hydroxybutyric acid