The S-oxidative degradation of a novel corticosteroid tipredane (INN). Part I: Preliminary investigations into the hydrogen peroxide S-oxidation of tipredane.
The C-17 dithioketal moiety of the corticosteroid tipredane (INN, I) has been shown to undergo peroxide oxidation yielding an array of sulphoxide epimers. All epimers have been isolated and characterized by spectroscopic techniques. Oxidation of the C-17 beta methylthio-substituent appeared to occur exclusively giving a 4:1 ratio of the S:R configuration at the sulphoxide moiety. Both methylthiosulphoxide epimers (V) have been shown to be susceptible to thermolysis yielding the monoethylthio- derivative (VI) via elimination of methylsulphenic acid. As expected from stereochemical considerations at the C-17 position the S epimer has been found to be more susceptible than its corresponding R epimer towards thermolysis. The monomethylthiosulphoxide epimers (III) were produced in a 1:1 ratio, indicating that they were formed from the oxidation of the corresponding monomethylthio- derivative (VII). This probably arose from the elimination of ethylsulphenic acid from the alpha-ethylthiosulphoxide (VIII).
Euerby
M R
MR
Analytical Chemistry Department, Fisons Pharmaceuticals PLC, Loughborough, Leicestershire, UK.
Hare
J
J
Nichols
S C
SC
D000287:Administration, Topical; D000730:Androstadienes / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006861:Hydrogen Peroxide / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014961:X-Ray Diffraction
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; C051756:tipredane; D006861:Hydrogen Peroxide