18-Vinyldeoxycorticosterone: a potent inhibitor of the bovine cytochrome P-45011β Original Research Article

18-Vinylprogesterone (18-VP) and 18-ethynylprogesterone (18-EP) have proved to be potent suicide inhibitors of P-45011β, the last enzyme of aldosterone biosynthesis (Delorme, C.; Piffeteau, A.; Viger, A.; Marquet, A. Eur. J. Biochem. 1995, 232, 247; Delorme, C.; Piffeteau, A.; Sobrio, F.; Marquet, A. Eur. J. Biochem. 1997, 248, 252). This paper describes the synthesis of 18-vinyldeoxycorticosterone (18-VDOC), an analogue of deoxycorticosterone (DOC), the physiological substrate of the enzyme, and the evaluation of its reversible inhibiting properties for deoxycorticosterone and corticosterone oxidation by the bovine enzyme. 18-VDOC has been obtained by hydroxylation at C-21 of a 18-VP precursor. Its reversible Ki values are, respectively, 0.3 μM for the 11β-hydroxylation and 0.8 μM for the 18-hydroxylation. Hence, 18-VDOC is the strongest competitive inhibitor of bovine P-45011β described so far, but in contrast with 18-VP, it does not inhibit more efficiently the 18-hydroxylation than the 11-hydroxylation.