Formamidobisabolene-based derivatives from a sponge Axinyssa sp.

Chemical examination of a Chinese sponge Axinyssa sp. resulted in the isolation of 12 new formamidobisabolene-based analogues named axinyssines A–L (1–12), along with a new natural product (13) and three known formamidobisabolenes (14–16). Their structures were determined on the basis of extensive NMR and mass spectroscopic analyses in association with ICD data, Mosher reaction and chemical conversion for the assignment of absolute configurations. All compounds were evaluated for antitumor and antimicrobial activities.     

Capisterones A and B from the tropical green alga Penicillus capitatus: unexpected anti-fungal defenses targeting the marine pathogen Lindra thallasiae

The mechanism by which marine algae show resistance to pathogenic microorganisms remains poorly understood. To examine the possible role that algal secondary metabolites play in the prevention of infection, we examined the abundant green alga Penicillus capitatus, one of the major shallow water algae found in the Tropical Atlantic Ocean. Both aqueous and EtOAc extracts of this alga were found to be potent inhibitors of the well-known marine algal pathogen Lindra thallasiae. Using L. thallasiae in bioassay-guided fractionation, we isolated two new triterpene sulfate esters, capisterones A (1) and B (2). The capisterones are potent inhibitors of L. thallasiae at natural and below natural concentrations. The structures of the capisterones, with relative stereochemistry only, were assigned by comprehensive spectral analyses that relied heavily on 2D NMR methods.     

Cytosporin-related compounds from the marine-derived fungus Eutypella scoparia

Chemical investigation of the culture broth of the fungus Eutypella scoparia ICB-OBX, isolated from the marine pulmonate mollusc Onchidium sp., led to the finding of novel compounds 1 and 2, structurally related to angiotensin II binding inhibitors cytosporins, along with unrelated known nitrogen metabolites (compounds 3-5). The structure and the relative stereochemistry of the novel metabolites were assigned mainly by a detailed analysis of two-dimensional NMR techniques whereas the absolute stereochemistry was proposed by modified Mosher's method. Compound 2 contains an unusual cyclic carbonate functionality that is rare among natural products.     

Karatungiols A and B, two novel antimicrobial polyol compounds, from the symbiotic marine dinoflagellate Amphidinium sp.

Karatungiols A (1) and B (2), two novel antimicrobial polyol compounds, were isolated from the cultivated symbiotic marine dinoflagellate Amphidinium sp. Their structures were elucidated based on spectroscopic analysis and degradation reactions. Karatungiols A (1) and B (2) consisted of a C69-linear chain with a ketone moiety, 24 or 25 hydroxyl groups, and two tetrahydropyran rings. Karatungiol A (1) exhibited antifungal activity against Aspergillus niger at 12 μg/disc and antiprotozoan activity against Trichomonas foetus at 1 μg/ml.     

Synthesis of the fungal natural product (−)-xylariamide A

The first synthesis of the fungal natural product (−)-xylariamide A 1 is reported. N,O-Bis(trimethylsilyl)acetamide induced coupling of d-tyrosine with (E)-but-2-enedioic acid 2,5-dioxo-pyrrolidin-1-yl ester methyl ester 5 produced the dechloro natural product 6, which was subsequently monochlorinated using oxone and KCl to yield synthetic 1. (−)-Xylariamide A 1, (+)-xylariamide A 2 and (−)-dechloroxylariamide A 6 displayed no cytotoxic or antimicrobial activity.     

New pyridoacridine alkaloids from the purple morph of the ascidian Cystodytes dellechiajei

Two new pyridoacridine alkaloids, 13-didemethylaminocycloshermilamine D (1) and demethyldeoxyamphimedine (2), were isolated from the purple chromotype of the Western Mediterranean ascidian Cystodytes dellechiajei. This morph also contained the known shermilamine B (3), kuanoniamine D (4), N-deacetylshermilamine B (5), N-deacetylkuanoniamine D (6), styelsamines C (7), and D (8). The structures of new compounds were elucidated on the basis of spectroscopic data. A hypothetic biosynthetic pathway from the tetracyclic styelsamine D (8) was proposed for both compounds 1 and 2 and their antimicrobial potential was evaluated.     

Didemnaketals D and E,bioactive terpenoids from a Red Sea ascidian Didemnum species

Two new spiroketals, didemnaketals D (1) and E (2) were isolated from a marine ascidian species belonging to the genus Didemnum. The structures of the compounds were elucidated by extensive 1D (¹H, ¹³C, and DEPT) and 2D (COSY, TOCSY, HSQC, HMBC, NOESY, and ROESY) NMR studies and high-resolution mass spectroscopic data. The new didemnaketals differ from the reported ones in which that they lack the methyl functionality at C-6 and the hydroxy moiety at C-21. Instead, they possess an ester moiety at C-6 in addition to new oxygen functionality at C-20 of the didemnaketals. Compounds 1 and 2 were evaluated for their protein kinase inhibitory activity against different kinases (CDK5, CK1, DyrK1A, and GSK3) at 10 μg/mL. Compounds 1 and 2 showed moderate activity against these kinases. In addition, the compounds displayed moderate antimicrobial activity against Staphylococcus aureus and Bacillus subtilis, respectively.     

Unusual octalactones from Corynespora cassiicola, an endophyte of Laguncularia racemosa

Chemical investigation of the EtOAc extract of the mangrove-derived endophyte Corynespora cassiicola, isolated from Laguncularia racemosa (Combretaceae), afforded five new secondary metabolites, named coryoctalactones A–E (1–5). The structures of the new compounds were determined on the basis of 1D- and 2D-NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of the side chain in 1–3 and 5 were tentatively deduced based on biogenetic consideration in comparison with xestodecalactones, previously isolated from C. cassiicola. All isolated compounds were evaluated for their antimicrobial, cytotoxic, and antitrypanosomal activities.     

Two novel 3,4-seco-trinorlanostane triterpenoids isolated from Ganoderma fornicatum

Two novel 3,4-seco-25,26,27-trinorlanostane triterpeniod compounds, fornicatins A and B (1 and 2) have been isolated from the fruiting body of G. fornicatum. The structural elucidation of 1 and 2 were accomplished by extensive NMR analysis. The relative stereochemistry of 2 was established by single crystal X-ray crystallography, which also confirmed the novel carbon skeleton of the new triterpenoid. An ether linkage of C-4 with C-7 in 1 is unprecedented in natural triterpenoids. Both compounds were tested for their inhibitory effects on rabbit platelet aggregation induced by PAF, ADP, or AA.     

Stereoselective total synthesis of ieodomycin C

A concise stereoselective synthesis of the marine natural product ieodomycin C (3) has been achieved from commercially available pyridinium-1-sulfonate (8) in eight linear steps and 14% overall yield. The key synthetic steps included a B-alkyl Suzuki–Miyaura cross-coupling reaction and an Evans–Nagao acetate aldol reaction. The same synthetic sequence was used for preparing the enantiomer of ieodomycin C (3). Our efforts confirmed the structure of the antibacterial natural product 3.     

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.     

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.     

Spironaamidine, a new spiroquinone-containing alkaloid from the marine sponge Leucetta microraphis

Spironaamidine (1), a unique spiroquinone-containing alkaloid, was isolated from the marine sponge, Leucetta microraphis, along with two known imidazole alkaloids, naamidine H (2) and (9E)-clathridine 9-N-(2-sulfoethyl)imine (3). Spironaamidine (1) showed antimicrobial activity against Bacillus cereus.     

Chloctanspirones A and B, novel chlorinated polyketides with an unprecedented skeleton, from marine sediment derived fungus Penicillium terrestre

Two novel chlorinated sorbicillinoids named chloctanspirones A (1) and B (2), possessing an unprecedented bicyclo[2.2.2]octane-2-spiro cyclohexane skeleton, together with their quasi-precursors terrestrols K (3) and L (4), two additional new chlorinated compounds, were isolated from a marine sediment derived fungus Penicillium terrestre. Their structures including absolute stereochemistries were elucidated by analysis of NMR, MS data, and TDDFT CD calculations. The cytotoxic effects of 1-4 were preliminarily evaluated in HL-60 and A-549 cells. Compound 1 was active against both HL-60 and A-549 cells with IC₅₀s 9.2 and 39.7 μM, respectively, while 2 showed weaker activity only against HL-60 cells (IC₅₀ 37.8 μM).     

Topsentiasterol sulfates with novel iodinated and chlorinated side chains from the marine sponge Topsentia sp.

Three new marine polar steroids, the first chlorine-containing steroid sulfate (1), topsentiasterol sulfate F (2) and the first natural iodinated steroid (3) have been isolated from the marine sponge Topsentia sp. The structures of 1-3 were elucidated using NMR and HRESIMS as well as by chemical correlation of 1 with previously known topsentiasterol sulfate D. Compound 1 proved to be an effective inhibitor of endo-1,3-β-d-glucanase from the marine mollusc Spisula sachalinensis.     

Novel prenylated and geranylated aromatic compounds isolated from Polysphondylium cellular slime molds

We have studied the diversity of secondary metabolites of cellular slime molds to utilize them as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium tenuissimum, we obtained five prenylated and geranylated aromatic compounds, Pt-1-5 (1-5). An additional aromatic compound, Ppc-1 (6), was isolated from Polysphondylium pseudo-candidum. The structures of these compounds were determined by spectral analysis, and synthetic routes to 4, 5, and 6 were developed. Compound 5 showed the glucose consumption-promotive activity on 3T3-L1 cells.     

Parviflorenes B-F, novel cytotoxic unsymmetrical sesquiterpene-dimers with three backbone skeletons from Curcuma parviflora

Five novel natural products classified as dimeric sesquiterpenes, named parviflorenes B-F (2-6), possessing three types of novel backbone frameworks, have been isolated from Curcuma parviflora (Zingiberaceae). The structures of 2-6 were elucidated by means of spectroscopic studies, and the structure of 2 was further unambiguously established by X-ray crystallographic analysis. Compounds 2, 4, and 6 have an unsymmetrical bis-cadinane skeleton, while compound 3 is a dimer of cadinane and iso-cadinane, and compound 5 possesses another novel carbon framework consisting of two cadinanes with different bond-connection. These new compounds with novel carbon skeletons showed cytotoxicity against tumor cell lines.     

Cyclopeptides and polyketides from coral-associated fungus, Aspergillus versicolor LCJ-5-4

Three new cyclopentapeptides, versicoloritides A-C (1-3), a new orcinol tetramer, tetraorcinol A (4), and two new lactones, versicolactones A and B (5 and 6) together with three known metabolites, diorcinol, glyantrypine, and cordyol C were isolated from the fermentation broth of the coral-associated fungus Aspergillus versicolor LCJ-5-4. Their structures were elucidated by spectroscopic and chemical methods. The new compounds 1-4 were evaluated for their radical-scavenging activity and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Enterobacter aerogenes, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans and cytotoxicity against P388 and Hela cell lines. Compound 4 showed weak radical-scavenging activity against the DPPH radical with an IC₅₀ value of 67 μM.     

Velutabularins A-J, phragmalin-type limonoids with novel cyclic moiety from Chukrasia tabularis var. velutina

Velutabularins A-J, ten novel phragmalin-type limonoids, were isolated from the stem bark of Chukrasia tabularis var. velutina. In structures of 1-6, the tetrahydrofuran ring from dehydration of OH-15 and OH-17, ring C and 13/14/18-cyclopropanyl moiety formed an unprecedented 8-oxatricyclo[4,3,1^1,6]decane. Compounds 7-10 are derivates of 1-6 opening the tetrahydrofuran ring. All of these compounds possess a novel C-16/C-30 δ-lactone ring, which were reported in phragmalins rarely. The structures of these novel compounds were elucidated based on extensive 1D and 2D spectroscopic analysis. The absolute configuration of 5 and 9 were determined by the calculated electronic circular dichroism (ECD) method. The anti-inflammatory activities of major compounds (2, 4, 5, 9) were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line.     

New diterpene pyrone-type compounds, metarhizins A and B, isolated from entomopathogenic fungus, Metarhizium flavoviride and their inhibitory effects on cellular proliferation

To date, entomopathogenic fungi have not been extensively examined by natural product chemists. In this study, we isolated novel pyrone diterpene-type compounds, metarhizins A (1) and B (2), from methanol extracts of entomopathogenic fungus, Metarhizium flavoviride. They showed potent and selective antiproliferative activity against both insect and human cancer cell lines. These results indicate that metarhizins A (1) and B (2) can be used as novel lead compounds for anti-cancer agents and probes for cell cycle regulation. To further investigate the structural requirements for this inhibitory activity, we synthesized many metarhizin derivatives and evaluated their antiproliferative activities.