New polyoxygenated ent-manoyl oxides obtained by biotransformation with filamentous fungi

Incubation of methyl (13R)-ent-16-hydroxy-8 alpha,13-epoxylabd-14-en-18-oate [4] with Curvularia lunata yielded ent-1 beta-hydroxy [6] and ent-6 beta-hydroxy [7] derivatives, and that of methyl (13S)-ent-16-dihydroxy-8 alpha,13-epoxylabd-14-en-18-oate [5] with the same organism gave ent-11 beta-hydroxy [8], ent-6 beta-hydroxy [9], and ent-6 beta,11 beta-dihydroxy [10] derivatives. The incubation of substrates 4 and 5 with Fusarium moniliforme afforded ent-1 beta-hydroxy derivatives (6 and 14, respectively). Cunninghamella elegans produced ent-3 beta-hydroxy, ent-1 beta-hydroxy and ent-1 beta,3 beta-dihydroxy derivatives, and led to epoxidation of the double bond of the substrates. In addition, ent-3 beta,11 alpha-dihydroxy (as the acetoxy derivative 17) and ent-3 beta,11 beta-dihydroxy [12] derivatives were isolated from incubations of substrates 4 and 5, respectively. Compounds 7, 9-11, 14, 16-18, and 21 were characterized as new polyoxygenated ent-manoyl oxides.