The selective deuteration of organic compounds offers great application opportunities either as drugs or diagnostic tools. The benefits of deuterium labeling have long been considered to improve the properties of drugs. While metabolic enzymes often transform drug molecules to inactive metabolites, the introduction of deuterium to drugs strengthens their resistance toward undesired metabolic degradation. As a breakthrough, in 2016, a deuterated drug developed by TEVA Pharmaceuticals, d6-tetrabenazine was approved to treat the symptoms of Huntington’s disease. Due to the significance of deuterated compounds, the development of efficient and selective deuteration methods attracted great interests. Most methods, however, do not conform to recent expectations and standards of sustainable synthesis; e.g. the metal deuteride reagents are used in excess and generate significant amount of toxic waste. In a recent publication we have introduced the environmentally benign Pd/Al-H2O catalytic system for simple, easy and convenient reduction of a broad range of organic substrates. In the present work we extend the application of this system for the selective H-D exchange of a variety of compounds simply replacing water with D2O thus its reaction with Al would produce D2 that will be utilized by the Pd catalyst for the H-D exchange. A range of substrates from amino acids and amines to esters and alcohols were successfully deuterated under microwave irradiation. The major advantages of this method are: (i) the combination Pd/C-Al-D2O that provides a safe way to produce D2 in situ and generates the non-toxic and recyclable aluminum oxide as the only waste, (ii) the availability of the catalyst that is ligand-free and provides excellent selectivity, (iii) a rapid synthesis ensured by the microwave irradiation. It is easy to conceive that the procedure outlined will contribute to improve H-D exchange reactions in drug design in terms of cost, time and environmental impact.

Preparation of deuterium labeled compounds by Pd/C-Al-D2O facilitated selective H-D exchange reactions

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.