Synthesis of enantio-manoyl oxides: Modifiers of the activity of adenylatecyclase enzyme

Cyclization of methyl ent-8 α-hydroxylabd-13(16),14-dien-18-oate with m-chloroperbenzoic acid gave methyl (13 S)- ent-16-hydroxy-8 α,13-epoxylabd-14-en-18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nigricans cultures produced the methyl (13 S)- ent-11 β,16-dihydroxy-8 α,13-epoxylabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13 S)- ent-3 β,16-dihydroxy-8 α,13-epoxilabd-14-en-18-oate, methyl (13 S)- ent-3 β,11 β,16-trihydroxy-8 α,13-epoxilabd-14-en-18-oate and the (14 S)- ent-3 β-hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13 S)- ent-16-hydroxy-3-oxo-8 α,13-epoxilabd-14-en-18-oate with R. nigricans produced ent-11 β-hydroxylation, reduction of the keto group at C-3 (to give 3 S-alcohol) and 14( S),15-epoxidation, which also rearranged to a spiro compound.