Synthesis and Pharmacology of Anti-inflammatory Steroidal Antedrugs

A study was conducted to demonstrate the synthesis of anti-inflammatory steroidal antedrugs. Prednisolene underwent significant oxidation with methanolic cupric acetate applying the procedure of Lewbart, Mattox, and Monder. It was observed that mild oxidation of prednisolene with methanolic cupric acetate for a short period resulted in aldehydes that gave methyl esters after being oxidized with KCN and MnO 2 in a mixture of methanol and acetic acid. It was suggested that the reaction proceeded through the formation of cyanohydrin, which was enolized to yeild bis-enol followed by β-elimination of benzoate, giving 17-deoxy-α-ketonitnile. The synthesis of 16-carboxylate ester was possible with the discovery of the key intermediates, such as 16,17-unsaturated corticosteroids. It was demonstrated that the 16-nitrile was the key intermediate for synthesizing the 17-hydroxy-16- carboxyesters.