Mechanism of base-catalyzed autooxidation of corticosteroids containing 20-keto-21-hydroxyl side chain

✍ Scribed by Min Li; Bin Chen; Stephanie Monteiro; Abu M. Rustum

• Book ID: 104096634
• Publisher: Elsevier Science
• Year: 2009
• Tongue: French
• Weight: 452 KB
• Volume: 50
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/j.tetlet.2009.05.074

✦ Synopsis

Corticosteroids and related compounds containing the 20-keto-21-hydroxyl side chain such as betamethasone, betamethasone 9,11-epoxide, dexamethasone, and dexamethasone 9,11-epoxide have been found to undergo facile autooxidation on the 1,3-dihydroxyacetone side chain of their D-rings under strong alkaline conditions to yield five main degradants (17-formyloxy-17-acid, 17-acid, 21-aldehyde, 20hydroxy-21-acid, and 17-ketone). The rate of the autooxidation was correlated with the strength and concentration of the base used in the reaction. A novel mechanism for the observed autooxidation is proposed, in which the facile oxidation of the presumed enolate (resulting from the carbanion at the 21-position) by molecular oxygen is the key step. The proposed autooxidation mechanism, supported by LC-MS isotope experiments using 18 O 2 as the oxidant, can satisfactorily explain the oxidative degradation patterns observed for corticosteroids containing the 20-keto-21-hydroxyl side chain.