Chiral liquid chromatography separation and chiroptical properties of the enantiomers of dimethyl α-hydroxyfarnesylphosphonate, a precursor of a farnesyl protein transferase inhibitor

The HPLC enantiomeric separation of racemic and non-racemic samples of dimethyl α-hydroxyfarnesylphosphonate (1) was accomplished using Chiralcel OD as chiral stationary phase. Single enantiomers were isolated by semipreparative HPLC and their CD spectra and optical rotations were measured. The method ascertains enantiomeric excess of 1, obtained by oxidation of dimethylfarnesylphosphonate with enantiopure oxaziridines, avoiding converting the enantiomers to diastereomers by the use of a chiral auxiliary. Stability of the solutions of 1 is strongly dependent on the nature of the solvent.