Chemicals labelled with the heavy hydrogen isotope deuterium (²H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed ²H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only ²H₂O (D₂O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed ²H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from ²H₂O solvent to NAD⁺, with H₂ gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.

Search

Refine Search

1 results in deuterated cofactors in Keywords: deuterated cofactors

Bringing Biocatalysis into the Deuteration Toolbox

1 results in Keywords: deuterated cofactors