Coumadin (warfarin) is an anticoagulation drug for the treatment and/or prevention of thromboembolic events. Maintaining an optimal drug dose is challenging due to high inter-individual variability in patient response and a narrow therapeutic range. We use warfarin metabolite profiles from patients to improve understanding of the link between metabolism and treatment response. Phase 1 metabolism produces a variety of hydroxywarfarins which are converted to their glucuronide derivatives in Phase 2. We have prepared 6-, 7-, and 4’-hydroxywarfarins with ee &gt;99% via an enantioselective, catalytic coupling. Borohydride reduction of the S-warfarin carbonyl produces two diastereomers, as does that of R-warfarin. These “warfarin alcohols” are also produced in vivo. We have separated the four enantiomers via TLC. Taken together, these efforts provide a simple and effective route to generate critical enantiomeric standards for identifying biomarkers to help predict patient Coumadin dose-responses.

Enantioselective synthesis and characterization of phase 1 warfarin metabolites

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.