Synthesis of Deuterated Cycrimine Based on Multiple Deuteration of Cycloalkane Carboxylic Acid

In recent years, deuterated pharmaceuticals (heavy drugs) have attracted significant attention as novel drug discovery modalities. While the stronger C–D bonds, as compared to C–H bonds, result in improved metabolic stability, the introduction of multiple deuterium atoms alters the physicochemical properties. Among the various methods developed for the synthesis of deuterated compounds, H/D exchange reactions are regarded as the most straightforward and useful. Herein, we developed a direct method for the multiple deuteration (H/D exchange reactions) of sodium cycloalkanecarboxylates bearing cyclopentane and cyclobutane rings using deuterium oxide, the most inexpensive deuterium source, in the presence of a Pt/C catalyst. Furthermore, deuterated cycrimine was synthesized from the deuterated sodium cyclopentanecarboxylate, and the effect of deuteration on lipophilicity was evaluated by a parallel artificial membrane permeability assay. Although no significant difference in lipophilicity was observed between the deuterated and hydrogenated forms, this study provides a useful method for the synthesis of deuterated compounds and a new synthetic approach to deuterated pharmaceuticals.