1H and 13C NMR chemical shift assignments and conformational analysis for the two diastereomers of the vitamin K epoxide reductase inhibitor brodifacoum

Proton and C-13 NMR chemical shifts and H-1-H-1 scalar couplings for the two diastereomers of the potent vitamin K epoxide M reductase (VKOR) inhibitor brodifacoum have been determined at 293 K from acetone solutions containing both diastereomers. To facilitate difficult assignments, homo- and heteronuclear correlation spectra were acquired at 750 and 900 MHz over 268-303 K temperature range. Conformations of both diastereomers inferred from the scalar couplings and 1-D NOE measurements reveal that one diastereomer (SS/RR) adopts a strained geometry in the cyclohexene ring system of the tetralin group. The NMR spectra also show evidence of line broadening due to conformational exchange at room temperature for the SR/RS diastereomer. These assignments and conformational analyses may be useful in studies of biomolecular interactions of brodifacoum with target proteins such as VKOR and in source determination of brodifacoum. Copyright (C) 2009 John Wiley & Sons, Ltd.