Biotransformation of 4beta-hydroxyeudesmane-1,6-dione by Gliocladium roseum and Exserohilum halodes.

Biotransformation of sesquiterpene 4beta-hydroxyeudesmane-1,6-dione by the filamentous fungi Gliocladium roseum and Exserohilum halodes was achieved. With Exserohilum halodes, only one metabolite was obtained, as a result of the regio- and stereoselective reduction of the keto group at C-1, which is difficult to achieve by chemical means. Five metabolites were produced with Gliocladium roseum, three of which, the 7alpha-hydroxylated, the 7alpha,11- and the 1alpha,8alpha-dihydroxylated derivatives, have not previously been reported. The hydroxylation at C-11 is the main action of this microorganism. These 11-hydroxylated compounds can be chemically transformed into 6beta,12-eudesmanolides.

Regioselective enzymatic acylations of polyhydroxylated eudesmanes: semisynthesis, theoretical calculations, and biotransformation of cyclic sulfites.

Different lipase enzymes have been tested in order to perform regioselective acetylations on the eudesmane tetrol from vulgarin. High yields (95%) of 1,12-diacetoxy derivative (4) were achieved in 1 h with Candida antarctica lipase (CAL). However, only the 12-acetyl derivative (6) was obtained in similar yield with Mucor miehei (MML) or Candida cylindracea (CCL) lipases. The enzymatic protection at C-1 and C-12 has been used to form eudesmane cyclic-sulfites between C-6 and C-4 atoms. The R/S-sulfur configuration has been assigned by means of the experimental and theoretical (13)C and (1)H NMR chemical shifts. The theoretical shifts were calculated using the GIAO method, with a MM+ geometry optimization followed by a single-point calculation at the B3LYP/6-31G(*) level (B3LYP/6-31G(*)//MM+). Moreover, B3LYP/6-31G(*) geometry optimizations were carried out to test the B3LYP/6-31G(*)//MM+ results, for the deacetylated sulfites (12 and 15). In addition to the delta(C) and delta(H) shifts, the (3)J(HH) coupling constants were also calculated and compared with the experimental values when available. Finally, different reactivities have been checked in both sulfites by biotransformation with Rhizopus nigricans. While the R-sulfite gave 2 alpha- and 11 beta-hydroxylated metabolites, the S-sulfite yielded only regioselective deacetylations. Furthermore, both sulfites showed different reactivities in redox processes.

Isolation of ani-hepatotoxic principle form the juice of Ecballium elaterium.

The antihepatotoxic activity of elaterium (dried juice of the fruits of Ecballium elaterium, Cucurbitaceae) and cucurbitacin B (isolated from the juice) was studied against CCl4-induced hepatotoxicity. Pre- and posttreatment with elaterium and cucurbitacin B reduced CCl4-hepatotoxicity, as shown reduction in the anormally increased sGPT levels. Posttreatment caused a significant reduction in the degree of steatosis observed inthe control group, treated only with CCl4. In conclusion, elaterium and cucurbitacin B had preventive and curative effects against CCl4-induced hepatotoxicity.

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.

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 with m-chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,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 (13S)-ent-11 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 beta,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-oxo-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-alcohol) and 14(S),15-epoxidation, which also rearranged to a spiro compound.

Antimicrobial activity of natural and semisynthetic diterpenoids from Sideritis spp.

The antimicrobial activity of 22 natural diterpenoids of endemic Sideritis from Eastern Andalusia (Spain) is described. Only ent-kaur-16-ene foliol and ent-beyer-15-ene isopusillatriol proved to be active towards Gram-positive and acid-fast bacteria. The introduction of a ketonic group at C-15 on ent-kaur-16-enic systems produced a remarkable degree of activity.