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

Abstract

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.

Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core

“…Unfortunately, these methods involve several drawbacks, such as the production of radioactive waste, the need for cryogenic conditions, and the large quantity of metal sludge produced [48]. Catalytic H–D exchange reactions between H 2 and D 2 O appear more feasible, but often do not yield sufficiently pure D 2 and require long reaction times [49,50,51,52,53,54]. Alternatively, the application of deuterated reagents and deuterated solvents as isotopic sources eliminates the hazards of gas handling, but the costs of these special conditions severely limit the practical applicability [55,56,57,58,59].…”

Synthesis, characterization, and catalytic activity of heterometallic ion-pair Ni/Mn and Ni/Zn complexes

“…H/D exchange is an important method for characterizing the conformational flexibility of β 2 -microglobulin amyloid fibrils at single residue resolution [3]. Furthermore, deuterated products have been found in drug discovery processes [4]. Therefore, there is interest in selective catalytic H/D exchange processes for the synthesis of deuterated products.…”

A simple route to deuterated polystyrene block copolymers by reverse iodine transfer polymerisation

“…The most common use of deuterated polymers is to gain contrast in neutron scattering experiments. [20][21][22][23][24][25][26] Other applications include the use of deuterated compounds in pharmacology to follow metabolism, [27][28][29][30][31][32] tracing biodegradation of hydrocarbons in water 33 and the use of deuterated compounds in nuclear fusion experiments. [34][35][36] Deuterated polystyrene (d-PS) is usually synthesised using living anionic polymerisation.…”