Chemical-microbiological synthesis of ent-13-epi-manoyl oxides with biological activities.

The biotransformation of ent-13-epi-3-keto manoyl oxide, which possesses antileishmania activity, with Curvularia lunata produced ent-6 beta-hydroxy, ent-1 alpha-hydroxy, ent-11 beta-hydroxy and delta 1-derivatives, as well as a reduction product a C-3 (S-alcohol) with another hydroxyl group at C-6 (ent-6 beta) or C-11 (ent-11 beta). The ent-6 beta-hydroxy and delta 1-derivatives inhibited growth of the pathogenic protozoa, Leishmania donovani. The biotransformation of ent-12 alpha-acetoxy-3 beta-hydroxy-13-epi-manoyl oxide and ent-3 beta-acetoxy-12 beta-dihydroxy-13-epi-manoyl oxide gave ent-3 eta,12 beta-dihydroxy-13-epi-manoyl oxide and ent-3 beta,6 beta,12 beta-trihydroxy-13-epi-manoyl oxide (trimanoyl). Both products increased the activity of adenylatecyclase.