Degradation of cloprednol in aqueous solution. The enolization step

Abstract

The degradation of the glucocorticoid cloprednol and its 21,21-dideuterio analogue was studied in aqueous solution at 60 /sup 0/C. The kinetic deuterium isotope effect was found to vary from 5.5 under acidic conditions to 1.0 under alkaline conditions, indicating a change in rate-determining step as a function of pH. Incorporation of hydrogen into the C-21 position of cloprednol in partially degraded samples occurred slowly or not at all under acidic conditions but occurred rapidly under alkaline conditions. These results are consistent with the formation of an obligatory enol intermediate in the degradation reaction of cloprednol and require a change in the rate-determining step from rate-determining enolization under acidic conditions to reversible enol formation under alkaline conditions. Prednisolone, hydrocortisone, and other glucocorticoids possessing the dihydroxyacetone group at C-17 are expected to behave similarly.