Investigations into the epimerisation of tipredane ethylsulphoxide diastereoisomers during chromatographic analysis on reversed-phase silica I. Investigations into the reaction mechanism

Abstract

The epimeric α-ethylsulphoxides of tipredane have been shown to undergo sulphoxide epimerisation and elimination of ethylsulphenic acid during reversed-phase (RP) HPLC, prior to the chromatographic separation. This has been shown to be promoted by increased oven temperature, acidic mobile phase, extended analysis time, column chemistry (i.e. silanol population and distribution) and increased metal content (i.e. iron(II) and titanium) of the RP stationary material. Their propensity to undergo such reactions is related to the facile C-17α C-S(O)Et bond breakage. Epimerisation and elimination have been postulated to arise via a common intermediate: an immobilised ethylsulphoxide-metal-geminal silanol complex.