Designing chemical systems for precision deuteration of medicinal building blocks.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39349937.
- Also identified by DOI 10.1038/s41467-024-52127-6 and PMC identifier 11442640.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Methods are lacking that can prepare deuterium-enriched building blocks, in the full range of deuterium substitution patterns at the isotopic purity levels demanded by pharmaceutical use. To that end, this work explores the regio- and stereoselective deuteration of tetrahydropyridine (THP), which is an attractive target for study due to the wide prevalence of piperidines in drugs. A series of d<sub>0</sub>-d<sub>8</sub> tetrahydropyridine isotopomers were synthesized by the stepwise treatment of a tungsten-complexed pyridinium salt with H<sup>-</sup>/D<sup>-</sup> and H<sup>+</sup>/D<sup>+</sup>. The resulting decomplexed THP isotopomers and isotopologues were analyzed via molecular rotational resonance (MRR) spectroscopy, a highly sensitive technique that distinguishes isotopomers and isotopologues by their unique moments of inertia. In order to demonstrate the medicinal relevance of this approach, eight unique deuterated isotopologues of erythro-methylphenidate were also prepared.
Medical subject headings
- Deuterium
- Pyridines
- Methylphenidate