Synthesis of deuterium-labelled drugs by hydrogen-deuterium (H-D) exchange using heterogeneous catalysis

Multi-deuterium incorporations into drugs, such as theophylline, caffeine, valpromide, phenytoin, and trimethoprim, were post-synthetically achieved by Pd/C-, Pt/C-, or/and Rh/C-catalyzed hydrogen-deuterium exchange reactions under neutral conditions using deuterium oxide as the deuterium source in the presence of hydrogen gas. The present study offers facile and convenient methods for the preparation of highly deuterated medicines, which are expected to be used as long-lasting medicines as well as internal standards for metabolic studies and for the quantitative analyses of the parent drugs.