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Synthesis of tritiated Cyclosporin A and FK‐506 by metal‐catalyzed hydrogen isotope exchange

“…4,[9][10][11][12] The specific activity was studied in relation to the reaction time (15-120 min), nature of the catalyst, catalyst-tosubstrate ratio, and temperature (100-2208C). The identity of the material was determined by co-chromatography with unlabeled reference material as well as by 1 H-and 3 H-NMR spectroscopy (Bruker AM-500.13 and 533.46 MHz, CDCl 3 as solvent and TMS as internal standard).…”

“…Several procedures have been developed for labeling of aromatic compounds by isotope exchange with tritiated water. 4 The traditional procedure consists in stirring at room temperature a mixture of catalyst, substrate, tritiated water, and dioxane in the reaction ampoule. Under these conditions the specific activity can be as high as 65 GBq/mmol.…”

“…5,6 The specific activities of the resulting preparations varied from 67 to 670 GBq/mmol. The dependence of the degree of isotope exchange on the nature of the catalyst, the ratio of components of the reaction mixture (PdO as tritiated water source, compound to be labeled, catalyst, dioxane, and triethylamine), temperature, and the reaction time were studied.…”

“…The dependence of the degree of isotope exchange on the nature of the catalyst, the ratio of components of the reaction mixture (PdO as tritiated water source, compound to be labeled, catalyst, dioxane, and triethylamine), temperature, and the reaction time were studied. Such reactions are normally completed within 30-180 min, the optimal catalysts for exchange are 5% PdO/Al 2 O 3 and 5% Pd/BaSO 4 , the optimal ratios of palladium oxide-catalyst-substance are (25-30) : (30-35) : (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), optimal solvent is a 10:1 dioxane-triethylamine mixture, and the optimal temperatures are in the range 60-2008C. 5,6 This approach was shown to be applicable for labeling of various compounds (Table 1).…”

“…Ltd.) was rather inert towards reduction by tritium gas (10% only was reduced). Therefore, the catalyst was pre-activated for 4 Tritium labeling of unsaturated compounds (I) and (II) on the activated catalyst at 1008C and higher in a mixture of triethylamine and dioxane produce a number of by-products. Isolation of the desired labeled product from such multi-component reaction mixtures is a demanding problem.…”