18-VINYLDEOXYCORTICOSTERONE - A POTENT INHIBITOR OF THE BOVINE CYTOCHROME P-450(11-BETA)

18-Vinylprogesterone (18-VP) and 18-ethynylprogesterone (18-EP) have p roved to be potent suicide inhibitors of P-450(11 beta), the last enzy me of aldosterone biosynthesis (Delorme, C.; Piffeteau, A.; Viger, A.; Marquet, A. fur. J. Biochem. 1995, 232, 247; Delorme, C.; Piffeteau, A.; Sobrio, F.; Marquet, A. fur. J. Biochem. 1997, 248, 252). This pap er describes the synthesis of 18-vinyldeoxycorticosterone (18-VDOC), a n analogue of deoxycorticosterone (DOC), the physiological substrate o f the enzyme, and the evaluation of its reversible inhibiting properti es 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 K-i values are, respectively, 0.3 mu M for t he 11 beta-hydroxylation and 0.8 mu M for the 18-hydroxylation. Hence, 18-VDOC is the strongest competitive inhibitor of bovine P-450(11 bet a) described so far, but in contrast with 18-VP, it does not inhibit m ore efficiently the 18-hydroxylation than the 11-hydroxylation, (C) 19 98 Elsevier Science Ltd. All rights reserved.