Epoxidation of ent-pimara-8(14),15-dien-19-oic acid by whole cells of the endophytic fungus Aspergillus sclerotiorum.

The diterpene ent-pimara-8(14),15-dien-19-oic acid (1) was converted into four oxidized diterpenes, 15,16-epoxy-ent-pimar-8(14)-en-19-oic acid (1a), 15,16-epoxy-17-hydrxy-ent-pimar-8(14)-en-19-oic acid (1b), 15,16-dihydroxy-ent-pimar-8(14)-en-19-oic acid (1c), and 15-oxo-16-hydroxy-ent-pimar-8(14)-en-19-oic acid (1d), when added to Aspergillus sclerotiorum cells growing in liquid cultures, being 1b and 1d non described substances. A. sclerotiorum oxidized the double-bound Δ15, letting intact the Δ8(14), differently from previous studies where another Aspergillus specie oxidized carbons from the tricyclic part of the same substrate 1. Abietic acid (2), a diterpene having two endocyclic C-C double-bounds (Δ7(8) and Δ13(14)) was used to challenge this putative regioselectivity. The fungus oxidized one of the methyl groups at C-13 in a similar way shown by diterpene 1, producing 16-hydroxyabietic acid (2a). The tblastn analyses of whole-genome contigs indicated that A. sclerotiorum contains an enzyme similar to CYP105A1 from Streptomyces griseolus. The ent-pimaric acid (1) and its derived products 1a-1d were tested for antiparasitic activities against Leishmania amazonensis and Trypanozoma cruzi.