Biosynthetic studies of novel polyketides from the marine sponge-derived fungus Stachylidium sp. 293K04.

The marilones and marilines are a new family of polyketide metabolites recently isolated from the marine-derived fungus Stachylidium sp. 293K04. They are characterized by a phthalide and phthalimidine skeleton, respectively. From a series of feeding experiments using 13C-labeled precursors we could outline the biogenetic origin of the basic carbon skeleton of marilone A and mariline B. Results established the tetraketide nature of the phthalide/phthalimidine nucleus including the involvement of a methylated acetate starter unit in polyketide biosynthesis, which is unique amongst fungal metabolites.

Unprecedented polyketides from a marine sponge-associated Stachylidium sp.

From the marine sponge-derived fungus Stachylidium sp. six novel phthalide-related compounds, cyclomarinone (1), maristachones A-E (2-5), and marilactone (6), were isolated. The structure of compound 1 comprises a hydroxycyclopentenone ring instead of the furanone ring characteristic for phthalides and represents a new carbon arrangement within polyketides. In the epimeric compounds 5a and 5b the phthalide (=isobenzofuranone) nucleus is modified to an isobenzofuran ring with ketal and acetal functionalities. Biosynthetically the structural skeletons of cyclomarinone (1) and maristachones A (2), C (4), D (5a), and E (5b) are most unusual due to the presence of an additional carbon atom when compared to the basic polyketide skeleton. This special biosynthetic feature also holds true for the likewise isolated polyketide marilactone (6).

Hydroxylated sclerosporin derivatives from the marine-derived fungus Cadophora malorum.

The marine-derived fungus Cadophora malorum was isolated from the green alga Enteromorpha sp. Growth on a biomalt medium supplemented with sea salt yielded an extract, from which we have isolated sclerosporin and four new hydroxylated sclerosporin derivatives, namely, 15-hydroxysclerosporin (2), 12-hydroxysclerosporin (3), 11-hydroxysclerosporin (4), and 8-hydroxysclerosporin (5). The compounds were evaluated in various biological activity assays. Compound 5 showed a weak fat-accumulation inhibitory activity against 3T3-L1 murine adipocytes.

Ten-membered lactones from the marine-derived fungus Curvularia sp.

Investigation of the secondary metabolites of the marine-derived fungus Curvularia sp. yielded four new 10-membered lactones (1-4), along with the known modiolide A (5). The structures of 1-4 were characterized on the basis of spectroscopic and MS data and resemble known 10-membered lactones, but feature modified oxidation patterns around their macrocycles.

Apralactone A and a New Stereochemical Class of Curvularins from the Marine-Derived Fungus Curvularia sp.

Chemical investigations of the cytotoxic extract of the marine-derived fungus Curvularia sp. (strain no. 768), isolated from the red alga Acanthophora spicifera, yielded the novel macrolide apralactone A (1), as well as the antipodes of curvularin macrolides 2-7. Compound 8, a dimeric curvularin was recognised as an artefact. The structures of 1-8 were elucidated by interpretation of their spectroscopic data (1D and 2D NMR, CD, MS, UV and IR). Apralactone A (1) is a 14-membered phenyl acetic acid macrolactone, and the first such compound with a 4-chromanone substructure. Compounds 1, 2, 4, 5 and 6 were found to be cytotoxic towards human tumor cell lines with mean IC50 values in the range of 1.25 to 30.06 µM.

Ascospiroketals A and B, unprecedented cycloethers from the marine-derived fungus Ascochyta salicorniae.

Chemical investigation of the marine-derived fungus Ascochyta salicorniae led to the isolation of two novel natural products, ascospiroketals A (1) and B (2). From a biosynthetic standpoint, the compounds possess new ring systems. [structure: see text].

Arugosins G and H: prenylated polyketides from the marine-derived fungus Emericellanidulans var. acristata.

The fungus Emericella nidulans var. acristata was isolated as an endophyte from a Mediterranean green alga. Cultivation of this fungus yielded two new compounds, arugosins G (1) and H (2), together with the known metabolites 3-9. Arugosins (1-4) are benzophenone derivatives, biosynthetically related to the xanthones 5, 6, and 9. The indole alkaloid 7 displayed antitumor activity in a panel of 36 human tumor cell lines, exhibiting a mean IC(50) value of 5.5 microg/mL in an in vitro survival and proliferation assay. Furthermore, compounds 3 and 4 showed moderate antitumor activity toward individual tumor cell lines. None of compounds 1-8 exhibited any immunostimulatory activity assessed as the capacity to induce cytokines in PBMCs from healthy donors.

Polyketides from the marine-derived fungus Ascochyta salicorniae and their potential to inhibit protein phosphatases.

Chemical investigation of the marine fungus Ascochyta salicorniae led to the isolation of two new epimeric compounds, ascolactones A (1) and B (2), in addition to the structurally-related polyketides hyalopyrone (3), ascochitine (4), ascochital (5) and ascosalipyrone (6). The absolute configurations of the epimeric compounds 1 and 2 were assigned as (1R,9R) and (1S,9R), respectively, through simulation of the chiroptical properties using quantum-chemical CD calculations, and chiral GC-MS subsequent to oxidative cleavage (Baeyer-Villiger oxidation) of the side chain. In silico screening using the PASS software identified some of the A. salicorniae compounds (1-6) as potential inhibitors of protein phosphatases. Compound was found to inhibit the enzymatic activity of MPtpB with an IC(50) value of 11.5 microM.