SYNTHESIS OF ENANTIO-MANOYL OXIDES - MODIFIERS OF THE ACTIVITY OF ADENYLATECYCLASE ENZYME

Cyclization of methyl ent-8 alpha-hydroxylabd-13(16),14-dien-18-oate w ith m-chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,1 3-epoxylabd-14-en-18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nig ricans cultures produced the methyl (13S)-ent-11 beta,16-dihydroxy-8 a lpha,13-epoxylabd-14-en-18-oate (carbomanoyl, which inhibits the activ ity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydr oxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 bet a,16-trihydroxy-8 alpha,13-epoxilabd-14-en-18-oate and the (14S)-ent-3 beta-hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13S)-ent-16-hydroxy-3-ox o-8 alpha,13-epoxilabd-14-en-18-oate with R. nigricans produced ent-11 beta-hydroxylation, reduction of the keto group at C-3 (to give 3S-al cohol) and 14(S),15-epoxidation, which also rearranged to a spiro comp ound.