Stereospecific syntheses of trans-vinyldioxidosqualene and beta-hydroxysulfide derivatives, as potent and time-dependent 2,3-oxidosqualene cyclase inhibitors

trans-Vinyldioxidosqualene and beta-hydroxysulfide derivatives were synthes ized stereospecifically and evaluated as inhibitors of animal and yeast oxi dosqualene cyclases. Only trans-vinyldioxidosqualene and 2,3-epoxy-vinyl-be ta-hydroxysulfides, having the reactive function at crucial positions 14,15 and 18,19, were active as inhibitors of animal and yeast cyclases. (14-tra ns)-28-Methylidene-2,3: 14, 15-dioxidoundecanorsqualene 27 was the most pot ent inhibitor of the series of pig liver cyclase, with an IC50 of 0.4 mu M, and it behaved also as the most active time-dependent inhibitor of the ani mal enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.