Abstract
The chemo/regioselective H-D exchange of amino acids and synthetic building blocks by an environmentally benign Pd/C-Al-D2O catalytic system is described. Due to the importance of isotope labeled compounds in medicinal chemistry and structural biology, notably their use as improved drug candidates and biological probes, the efficient and selective deuteration methods are of great interest. The approach is based on selective H-D exchange reactions where the deuterium source is simple D2O. D2 gas is generated in situ from the reaction of aluminum and D2O, while the commercially available palladium catalyst assists the H-D exchange reaction. The high selectivity and efficiency, as well as the simplicity and safe nature of the procedure make this method an environmentally benign alternative to current alternatives.
Highlights
The selective H-D exchange of organic compounds, such as amines, alcohols or amino acids, offers great application opportunities either as drugs or as diagnostic tools
The benefits of deuterium labeling have long been considered to improve the properties of drugs [1]
While metabolic enzymes have the ability to transform drug molecules to inactive metabolites, the introduction of deuterium to drugs appears to strengthen their resistance toward metabolic degradation due to the improved stability of the deuteriumcarbon bond that is six to ten times stronger than the carbon-hydrogen counterpart [2]
Summary
The selective H-D exchange of organic compounds, such as amines, alcohols or amino acids, offers great application opportunities either as drugs or as diagnostic tools. The benefits of deuterium labeling have long been considered to improve the properties of drugs [1]. While metabolic enzymes (e.g., proteases) have the ability to transform drug molecules to inactive metabolites, the introduction of deuterium to drugs appears to strengthen their resistance toward metabolic degradation due to the improved stability of the deuteriumcarbon bond that is six to ten times stronger than the carbon-hydrogen counterpart [2]. The higher stability of the deuterated drug provides longer lasting effects, which allows lower dosage, likely causing fewer side effects [3,4]. The deuterium introduced on the methoxy groups of the tetrahydroisoquinoline ring appears to prevent the cleavage of these substituents that leads to the inactive form of the drug [7]
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