Modern methods for the synthesis of biologically active compounds labeled with hydrogen isotopes

Abstract

The review addresses methods for the introduction of hydrogen isotopes into organic compounds, which are then used as labeled building blocks in the synthesis of biologically active products. Hydrogen isotopes are introduced by either isotope exchange or chemical reactions. If a carbonyl group is present in the precursor of the biologically active compound, deuterium can be introduced both through isotope exchange and via the reduction of the ketone group. Labeled reagents such as [³H]methyl nosylate are also used to obtain labeled oligonucleotides. The introduction of hydrogen isotopes into estrone is performed using isotope exchange both in the solid state and in solution (D₂O, CF₃COOD). The replacement of the iodine atom with deuterium gives labeled analogs of xanthine, steroids, adamantane, carbohydrates, and other compounds. In some cases, to activate deuteration, deuterated silanes were synthesized and catalytic systems such as AgCO₃/PPh₃/K₂CO₃, Rh nanoparticles, and Pt^II-based catalysts were used. Issues related to hydrogen spillover are discussed in the context of solid-phase isotope exchange.