A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone

Spironolactone is a renal competitive aldosterone antagonist. One of its most important metabolite is the 7α-methylthio spironolactone: thus it is very important to have an efficient and safe access to this compound, for pharmacokinetic studies. In this context, we synthesized this metabolite by thioalkylation of 7α-thio spironolactone using Hünig’s base with a very good yield. We also used our procedure to prepare, with an easy work-up and high yields, 7α-thioether and thioester derivatives of spironolactone, that could be useful for further Structure–Activity Relationships studies.

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► Efficient synthesis of the 7α-methylthioether metabolite of spironolactone.
► Green approach of 7α-thioether and thioester spironolactone derivatives.
► Small library of C19 steroids, having a spirannic γ-lactone at the C-17.