Synthesis of tritium- and deuterium-labeled budesonide

Tritium-labeled budesonide was prepared by the selective reduction of a double bond in the butenylenedioxy side chain using carrier-free tritium and palladium on carbon as a catalyst in absolute ethanol. Although the reduction gave a mixture of the desired product and the expected byproducts resulting from over reduction of the other double bonds in ring A, the desired tritium-labeled budesonide was easily isolated by reverse phase HPLC and with specific activity of 54 Ci/mmol. [D8]-budesonide was prepared from 16α-hydroxyprednisolone and D8-butyraldehyde in 1,4-dioxane in the presence of perchloric acid. The isotopic enrichment was found to be more than 99 atom% D. Copyright © 2008 John Wiley & Sons, Ltd.