Deuterium-Enabled Chiral Switching (DECS) Yields Chirally Pure Drugs from Chemically Interconverting Racemates

Abstract

Separation of the preferred enantiomer from racemic mixtures, i.e. “chiral switching,” often improves efficacy and reduces toxicity. However, this strategy is not applicable for all chiral compounds—particularly for molecules with hydrogen-containing chiral centers, which can be prone to rapid stereoisomerization. Deuterium incorporation can stabilize such chiral centers while retaining the pharmacologic characteristics of the parent racemic mixture, thereby enabling their “chiral switching”, changing the drug from a racemate to a single enantiomer. We describe “deuterium-enabled chiral switching” (DECS) as a means of improving on the therapeutic promise of chemically unstable racemic drugs and demonstrate its utility with the isolation and characterization of stable preferred enantiomers of thalidomide and thiazolidinedione (TZD) analogs.