Stereospecific synthesis of trans-vinyl dioxidosqualene and b-hydrosulfide derivatives, as potent and time-dependent 2,3-oxidosqualene cyclase inhibitors

trans-Vinyldioxidosqualene and beta-hydroxysulfide derivatives were synthesized stereospecifically and evaluated as inhibitors of animal and yeast oxidosqualene cyclases. Only trans-vinyldioxidosqualene and 2,3-epoxy-vinyl-beta-hydroxysulfides, having the reactive function at crucial positions 14,15 and 18,19, were active as inhibitors of animal and yeast cyclases. (14-trans)-28-Methylidene-2,3: 14, 15-dioxidoundecanorsqualene 27 was the most potent 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 animal enzyme.