Dolastanes from the brown alga Dilophus spiralis: absolute stereochemistry and evaluation of cytotoxicity

Five new dolastanes (1-5) were isolated from the brown alga Dilophus spiralis. The structural elucidation of the isolated compounds and the assignment of relative stereochemistry were based on analyses of their spectroscopic data. The structure proposed for 1 was confirmed by single crystal X-ray diffraction analysis, whereas its absolute stereochemistry was determined using the modified Mosher's method. The cytotoxicity of 1-4 was evaluated against seven cell lines.     

Dilospiranes A and B: diterpenes featuring novel carbocyclic units from the brown alga Dilophus spiralis

Dilospiranes A and B (1 and 2), two diterpenes featuring unprecedented carbocycles, were isolated from the organic extract of the brown alga Dilophus spiralis, collected from the coast of Elafonissos Island, Greece. The structures and the relative configurations of the isolated natural products were determined on the basis of extensive analyses of their spectroscopic data.     

New cytotoxic sesquiterpenes from the red algae Laurencia obtusa and Laurencia microcladia

Three new sesquiterpenes (1-3), along with five known (5-9), were isolated from the organic extract of the red alga Laurencia obtusa, collected from the coastal rocks of Serifos in the Aegean Sea. A new dimeric sesquiterpene of the cyclolaurane-type (4) along with four previously reported (7, 10-12) metabolites, were isolated from the extract of Laurencia microcladia, collected at Chios island in the North Aegean Sea. The structures and the relative stereochemistry of the compounds are proposed on the basis of their spectral data. The cytotoxicity of the isolated metabolites was evaluated against several cell lines including human tumor cell lines.     

Five novel norcembranoids from Sinularia leptoclados and S. parva

Three new norcembrane-based diterpenoids, leptocladolides A (1), B (4) and C (5), along with five known metabolites 6-10, have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados. Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1-epi-leptocladolide A (2) and 7E-leptocladolide A (3), in addition to 1 and 7. The structures of new metabolites 1-5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.     

Two novel tricyclic diterpenoids from Isodon rubescens var. taihangensis

Two novel tricyclic diterpenoids rubescensins U (1) and V (2) were isolated from the leaves of Isodon rubescens var. taihangensis. They were elucidated as a 8,15-seco-ent-kauranoid and an ent-abietanoid, respectively, by 1D and 2D NMR spectra, and single crystal X-ray analysis. Compound 1 is the first example of an 8,15-seco-ent-kaurane from the plants genus Isodon. A discussion of their biogenesis is described.     

Pressurized fluid extraction of carotenoids from Haematococcus pluvialis and Dunaliella salina and kavalactones from Piper methysticum

Pressurized fluid extraction (PFE) was examined as an alternative technology for the extraction of carotenoids in the green algae Haematococcus pluvialis and Dunaliella salina and kavalactones in Piper methysticum. The extraction process was optimized by varying the key extraction factors of solvent, sample-solvent ratio, temperature, and time. The selectivity and efficiency of extraction parameters were determined with high performance liquid chromatography (LC) and LC-mass spectrometry (LC-MS). Results showed that PFE utilization of conventional solvents under controlled temperature and pressure in an oxygen and light-free environment could result in the use of less solvent in a shorter period of time. PFE showed higher or equal extraction efficiencies as compared with traditional solvent extractions while maintaining the integrity of chemical components. PFE showed high potential for extraction of natural products and nutraceuticals, particularly labile and light sensitive chemicals.     

3,4-seco-Diterpenoids from Trigonostemon flavidus

Phytochemical investigation on the stems of Trigonostemon flavidus resulted in the isolation of five new 3,4-seco-diterpenoids, trigoflavidones A-E (1-5), structurally related to the main co-occurring known 3,4-seco-sonderianic acid (6) and 3,4-seco-sonderianol (7). Compound 4 possesses new 3,4-seco rearranged ent-pimarane skeletal type, characteristic of a vinyl group at C-8, while 5 features a unique five-membered ring (C₁) fused with a cyclopropane ring (C₂). The structures of the new compounds were established by a combination of spectroscopic data and computational methods. Compounds 1-7 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines.     

6-endo Versus 5-exo radical cyclization: streamlined syntheses of carbahexopyranoses and derivatives by 6-endo-trig radical cyclization

Three factors that can direct 6-endo radical cyclization over 5-exo ring closure: substitution at C-5, vinyl radical cyclization and ring strain, have been considered in the context of the preparation of carbapyranoses from carbohydrate derivatives. As a result, alkyl radicals in substrates containing a strain inducing 2,3-O-isopropylidene ring, and vinyl radical in non-strained compounds undergo a completely regioselective 6-endo-trig ring closure leading to carbasugar derivatives.     

Trichiol and 3-epitrichiol acetate, novel cytotoxic sterols with an unprecedented 2,6-dioxabicyclo[2.2.2]octan-3-one ring system from the myxomycete Trichia favoginea var. persimilis

Trichiol (1) and 3-epitrichiol acetate (2), two new sterols, have been isolated from field-collected fruit bodies of the myxomycete, Trichia favoginea var. persimilis, and their structures elucidated by spectral data. Trichiol (1) and 3-epitrichiol acetate (2) possess an unprecedented 2,6-dioxabicyclo[2.2.2]octan-3-one ring system. Trichiol (1) was cytotoxic against HeLa cells, while compound 2 proved to exhibit reversal effect against TNF-related apoptosis inducing ligand (TRAIL)-resistant Jurkat cell lines.     

Atomarianones A and B: two cytotoxic meroditerpenes from the brown alga Taonia atomaria

Two novel cyclized meroditerpenoids atomarianones A, and B (1 and 2), were isolated from the organic extract of the brown alga Taonia atomaria collected at Serifos island in the Central Aegean Sea. This is only the second report on metabolites having a functionalized indane moiety instead of a benzofurano- or a benzopyrano-ring connecting their aromatic and diterpenoid parts. Atomarianone A contains an unprecedented cis B-C ring fusion while atomarianone B is the epimer of A at C-7. Both metabolites were found to exhibit significant cytotoxic activity against two lung cancer cell lines.     

Biotransformation of sinapic acid by the green algae Stichococcus bacillaris 155LTAP and Ankistrodesmus braunii C202.7a

Sinapic acid was bioconverted by the green alga Stichococcus bacillaris into 4-hydroxy-3,5-dimethoxybenzoic acid, 4-hydroxy-3,5-dimethoxybenzaldehyde and 4-hydroxy-3,5-dimethoxybenzylic alcohol. Incubation of sinapic acid in a culture of the alga Ankistrodesmus braunii gave 3,6-dihydroxy-2,4-dimethoxy-7H-benzocyclohepten-7-one, a new compound formed by bioconversion of thomasidioic acid, the primary oxidative product of sinapic acid.     

Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa

Chemical investigation of the endophytic fungus Diaporthe melonis, isolated from Annona squamosa, yielded two new dihydroanthracenone atropodiastereomers, diaporthemins A (1) and B (2), together with the known flavomannin-6,6′-di-O-methyl ether (3). The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopy, as well as by high resolution mass spectrometry and by CD spectroscopy. Compounds 1–3 were tested for their antimicrobial activity against a multi-resistant clinical isolate of Staphylococcus aureus 25697, a susceptible reference strain of S. aureus ATCC 29213 and against Streptococcus pneumoniae ATCC 49619. Compound 3 strongly inhibited S. pneumonia growth with a MIC value of 2 μg/mL, and showed moderate activity against the S. aureus multi-resistant clinical isolate and susceptible reference strain (MIC 32 μg/mL), whereas 1 and 2 were not active against the tested strains.     

Three new Lycopodium alkaloids from Huperzia carinata and Huperzia squarrosa

Eleven Lycopodium alkaloids with lycodine-type, lycopodine-type, and fawcettimine-related skeletons were isolated from the whole plants of Huperzia carinata (Desv. Ex. Poir.) Trevis and Huperzia squarrosa (G. Forst) Trevis (Huperziaceae). Among them, 8,15-dihydrohuperzine A (2), lycocarinatine A (3), and lycoposerramine U N-oxide (11) are new compounds. The structures of these new alkaloids were elucidated on the basis of 2D NMR correlations. Some of these isolated alkaloids were assayed for acetylcholinesterase (AChE) inhibitory activity.     

Banchromene and other secondary metabolites from the endophytic fungus Fusarium sp. obtained from Piper guineense inhibit the motility of phytopathogenic Plasmopara viticola zoospores

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1–4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5 μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10 μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola.     

Polyhydroxylated macrolide isolated from the endophytic fungus Pestalotiopsis mangiferae

A new polyhydroxylated macrolide, named mangiferaelactone (1) was isolated from a solid culture of the endophytic fungus Pestalotiopsis manguiferae, together with ten known compounds [(6S,1′S)-LL-P880α; (6S,1′S,2′R)-LL-P880β; (1′S,2′R)-LL-880γ; (1′R)-dehydropestalotin; (−)-5-carboxylmellein; (−)-5-methylmellein; (−)-5-hydroxylmethylmellein; arabenoic acid; 5,6-dihydro-4-methoxy-2H-pyran-2-one; and the (−)-2-hexylidene-3-methylsuccinic acid]. P. manguiferae was isolated from Hyptis dilatata, a small shrub common in the central region of Panama. The structure of compound 1 was elucidated by a combination of spectroscopic methods (IR, MS, optical rotation, 1D and 2D NMR spectroscopy). The absolute configuration of 1 was established as 4R,7R,8R,9S by application of vibrational circular dichroism (VCD). Compound 1 showed a minimum inhibitory concentration (MIC) of 1.6863 mg/mL against Listeria monocytogenes, and 0.5529 mg/mL against Bacillus cereus. No activity was observed for compound 1 against Plasmodium falciparum or Trypanosoma cruzi; likewise, no cytotoxic activity was observed against A2058 and H522-T1 cells.     

Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).     

Overlapping chemical and genetic diversity in Ligularia lamarum and Ligularia subspicata. Isolation of ten new eremophilanes and a new seco-bakkane compound

Root chemicals and DNA sequences were analyzed for Ligularialamarum samples collected in Yunnan and Sichuan Provinces of China and the relationship between the plant and Ligulariasubspicata, its taxonomically closest species, was examined. Both species produce furanoeremophilanes and eremophilan-8-one derivatives as the major components. Eleven new compounds, including a new seco-bakkane compound, were isolated. The two species were found to harbor overlapping intra-specific diversities with respect to the chemicals and the DNA sequences.     

Further syphonosides from the sea hare Syphonota geographica and the sea-grass Halophila stipulacea

The unusual structural features of syphonoside (1), recently reported from the marine mollusc Syphonota geographica and its prey Halophila stipulacea, stimulated further investigations on the minor secondary metabolites of both organisms. The three novel macrocyclic glycoterpenoids 2-4, structurally related to the main co-occurring metabolite 1, have been isolated and chemically characterized mainly by NMR spectroscopic techniques and degradation methods. Compounds 2 and 3 were found only in the mollusc whereas compound 4 was isolated in trace quantities exclusively from the sea-grass.     

Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.

Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC–ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1–3 and synthetic analogues 1a–e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD₉₉ 31 μg/mL), with preliminary structure–activity relationship investigations confirming the importance of the N-acyl side chain.     

Infectopyrone, a potential mycotoxin from Alternaria infectoria

A new metabolite, infectopyrone (1), has been isolated from the filamentous fungus Alternaria infectoria. The structure of 1 was elucidated by analysis of 2D NMR spectroscopic data. Compound 1 is an α-pyrone resembling known toxins, and is a useful phenotaxonomic marker for the A. infectoria species-group. Infectopyrone (1) was also produced by species within Stemphyllium and Ulocladium, and found in mouldy food.