Synthesis of tritium-labelled biologically active analogues of progesterone by selective hydrogenation of 16α,17α-cyclohex-3′-en-pregna-1,4-dien-3,20-dione

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

“…Liquid‐phase methods have advantages in the hydrogenation and dehalogenation of thermally labile bioactive compounds only, especially when a high degree of selectivity is required 54–59. The compounds labelled using these methods have a high specific radioactivity (40–55 Ci/mmol per one reduced carbon–carbon double bond) are obtained in good yield and contain label in preselected positions only.…”

Pregna-D′-pentaranes, progestins and antiprogestins: I. Separation of biological functions of steroid hormones

“…The tritium-labeled analogues of pentaranes (Va) and (IV) were obtained by the catalytic homogeneous or heterogeneous hydrogenation with gaseous tritium of their D'-ring-unsaturated precursors (XIVa) [20] and (XVII) [27], respectively. The labeled derivatives (XXIV), (XLIV), and (XLVII) were obtained from the corresponding 1,2-dehydroprecursors (XXV) and (XXVI) using the subsequent separation of the resulting tritiated pentaranes by HPLC [28,29]. 16α,17α-[ 3 H]Cyclopropanoprogesteron (II) was similarly obtained from the corresponding 1,2-dehydroprecursor [20].…”

“…These regularities could only be revealed after a deep insight into the mechanism of the hormonal action of progestins in order to establish the homogeneity of the population of the plasmatic (nuclear) progesterone receptor that mediates the transfer of hormonal signal, the uniformity or branching of this signal, and the dependence of the expression of the corresponding gene on the structure of steroid ligand. This study became possible after the preparation of a set of 3 H-labeled compounds with the separated biological functions, which can play the role of a convenient instrument for studying the mechanisms of accomplishment of these functions [20,[27][28][29].…”

Solid-phase method for tritium labelling of biologically active compounds

“…Only several percent of the 5a-isomer could be isolated from the reaction mixture; preparative amounts of this compound (a 1 : 3 ratio in the reaction mixture) have been obtained by using solid-phase hydrogenation. 112 This difference can be explained by the fact that the liquid-phase hydrogenation proceeds in the active sites of the catalyst, while in the solid-phase process, atoms of the metal catalyst generate activated tritium species, which react with a steroid molecule. Evidently, when the steroid is adsorbed on the catalyst active sites during hydrogenation in solution, the influence of the steric factors is maximum; however, if the active species of tritium attack the double bonds of the substrate molecule adsorbed on a support, the formation of 5a-isomers is more likely.…”