THE S-OXIDATIVE DEGRADATION OF A NOVEL CORTICOSTEROID TIPREDANE (INN).2. DETAILED INVESTIGATIONS INTO THE PRIMARY S-OXIDATION OF TIPREDANEUSING ACHIRAL OXIDANTS

The C-17 dithioketal moiety of the corticosteroid tipredane (INN,I) ha s been shown to undergo site and stereoselective S-oxidations with a r ange of achiral oxidants. S-Oxidation was favoured on the methylthio s ubstitutent (beta-plane) in preference to the ethylthio substituent (a lpha-plane) in a ratio of 1.8-3.5:1. S-Oxidation on both substituents appeared to be stereoselective yielding an approximate ratio of 4:1 an d 1:3.5-6 for the S-:R-methyl and ethylsulphoxide diastereoisomers, (I I and VI) respectively. The preferred sites for S-oxidation have been explained in terms of the preferred rotamers of the C-17 substituents and the steric factors imposed on the attack of the oxidant on the lon e pair of electrons at each sulphur atom. Optimized HPLC conditions us ing a Hypersil ODS column and an acetonitrile-0.025 M NH4OAc pH 7.2 gr adient at 26 degrees C were developed to prevent degradation of the et hylsulphoxide diastereoisomers (VI) occurring during chromatographic a nalysis, via elimination of ethylsulphenic acid to yield the correspon ding C-17 vinylmethylthio derivative (VII).