Solid‐phase reactions as approach to the synthesis of organic compounds labelled with tritium

Abstract

The solid-phase method for hydrogenolysis, hydrogenation and isotope exchange reactions is described. Its potential for tritium labelling of organic compounds including lipids, nucleotides, amino acids, peptides and pharmaceuticals is demonstrated. The influence of the reaction conditions on the yield and specific radioactivity of the labelled compounds is considered. It is shown that results can be interpreted by the dependence of tritium spillover reactions on the nature of the initial compound and other factors.

The efficiency of solvent‐free catalyst systems in the synthesis of tritium‐labelled biologically active compounds

“…Methods involving the use of solvent‐free catalyst systems have been extensively used to prepare isotopically labelled compounds 5. This paper presents an overview of recent achievements in this field.…”

“…In addition to the recently verified possibility of solid‐phase selective hydrogenation and dehalogenation,5 the regioselectivity (an uneven distribution of the isotopic label across different positions of the substrate molecule) of tritium introduction by means of this method should be taken into account in the optimization of reaction conditions. The main feature 6 of these reactions is the increased mobility of hydrogen on inert supports (the support is defined as inert if no noticeable isotopic exchange occurs between the tritium donor and the labelling substrate in the absence of the supported metal‐catalyst).…”

“…In a previous overview it was reported that solid‐phase reactions are subjected to different laws and have a different mechanism than reactions in solution 5. A ‘capacitor model’ of solid‐phase reactions has been described that explains the basic rules of introducing a tritium label into organic compounds using solvent‐free catalyst systems 22.…”

“…In the first case, isotopic exchange occurs primarily through positive tritium or deuterium ions (usually below 200°C),1, 2, 5 and therefore the label usually gets included in the fragment that is more liable to electrophilic substitution. Mass spectrometry results confirmed that the bulk of the deuterium (over 80%) in the maraviroc molecule is included in the benzyl section and in the substituents of the triazole section (Table 2).…”

50th anniversary special issue, in memoriam John Jones

“…8 Myasoedov 9 describes a technique that he and his colleagues have been developing for many years and which is high-temperature solid-state catalytic isotopic exchange (HSCIE), which is very useful for the synthesis of tritiated-labelled compounds and especially for complex molecules. 9 Dollé 10 describes the development of PET chemistry at the Hopital Frédéric Joliot in Orsay, France, one of the world's first PET centres. 10 Susan 11 outlines the history of the International Isotope Society, to the development of which he has made a major contribution.…”