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.     

Ircinamine B, bioactive alkaloid from marine sponge Dactylia sp.

Ircinamine B was isolated from the marine sponge Dactylia sp., which was collected at Cape Sada in Japan. Based on extensive spectral analysis, the structures of the isolated metabolites were established. This novel compound showed moderate activity against the murine leukemia cell line P388 (IC₅₀ 0.28 μg/mL).     

Cyclic tetrapeptides from marine bacteria associated with the seaweed Diginea sp. and the sponge Halisarca ectofibrosa

A Pseudomonas sp. was cultured which was associated with the Japanese seaweed Diginea sp. Crude extracts prepared from this bacterial culture were found to inhibit the growth of other marine bacterial strains. From this bacterial culture, two new peptides cyclo-[phenylalanyl-prolyl-leucyl-prolyl] (3) and cyclo-[isoleucyl-prolyl-leucyl-alanyl] (4) have been isolated together with two known peptides (1) and (2). The crude extract from a culture of Pseudoalteromonas sp. associated with the Thai sponge Halisarca ectofibrosa was found to inhibit the growth of Bacillus subtilis and Vibrio anguillarum. Isolation studies yielded a fraction containing two peptides that were identified as cyclo-[phenylalanyl-leucyl]₂ (5) and cyclo-[leucyl-isoleucyl]₂ (6) by means of LC-MS and 2D NMR data. Absolute stereochemistry was confirmed by the synthesis of cyclo-[l-phenylalanyl-l-leucyl]₂. Peptides (1)-(3) were also isolated from this bacterial strain. None of the individual peptides isolated in this study showed antibiotic activity.     

Fascioquinols A-F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.

Chemical investigation of a southern Australian deep-water marine sponge, Fasciospongia sp., returned the new meroterpene sulfate fascioquinol A (1) together with a series of acid mediated hydrolysis/cyclization products, fascioquinols B (2), C (3) and D (4), and strongylophorine-22 (5). Additional co-metabolites include the new meroterpenes fascioquinol E (6) and fascioquinol F (8), together with the known sponge metabolite geranylgeranyl 1,4-hydroquinone (7). Structures were assigned to 1-8 on the basis of detailed spectroscopic analysis, chemical interconversion, mechanistic and biosynthetic considerations, and literature comparisons. The known 1,4-hydroquinone 7 was identified as the dominant cytotoxic principle in the Fasciospongia sp. extract, with selective inhibitory activity against gastric adenocarcinoma (AGS, IC₅₀ 8 μM) and neuroblastoma (SH-SY5Y, IC₅₀ 4 μM) cell lines. By contrast, while the fascioquinols displayed little or no inhibitory activity towards human cell lines, 1 and 2 displayed promising Gram-positive selective antibacterial activity towards Staphylococcus aureus (IC₅₀ 0.9-2.5 μM) and Bacillus subtilis (IC₅₀ 0.3-7.0 μM).     

Bromine-containing alkaloids from the marine sponge Penares sp.

Two new unusual alkaloids were isolated from the sponge Penares sp., collected from Viet Nam waters (the South China Sea). The structures of these compounds were established by analysis of 1D, 2D NMR (¹H-¹H COSY, DEPT, HSQC, HMBC, H2BC, and NOE), and MS data. Compound 1 shows moderate cytotoxicity against the human tumor cells HL-60 and HeLa.     

Novel alkaloids of the aaptamine class from an Indonesian marine sponge of the genus Xestospongia

Four novel alkaloids of the aaptamine class have been isolated in addition to the known aaptamine, isoaaptamine, demethyl(oxy)aaptamine and its dimethylketal from an unidentified species of Indonesian marine sponge of the genus Xestospongia. Their structures were elucidated on the basis of detailed 1D and 2D NMR spectroscopic data. Their antimicrobial activity was tested towards Gram (+) (S. aureus), Gram (−) (E. coli, V. anguillarum) bacterial strains, a fungus (C. tropicalis); their cytotoxic activity was evaluated against KB cells.     

Untenolide A, a new polyketide from an Okinawan marine sponge Plakortis sp.

A new polyketide, untenolide A (1), has been isolated from an Okinawan marine sponge Plakortis species, and the structure was elucidated from spectroscopic data and X-ray analysis. Untenolide A (1) is a new polyketide possessing a fused-pentacyclic skeleton with two hexadecanyl chains.     

Nitrogenous sesquiterpenes from the Thai marine sponge Halichondria sp.

Five nitrogenous sesquiterpenes having an isonitrile [(−)-axisonitrile-3], a formamide [(+)-axamide-3, axamide-2 and (3S^*,5R^*,6R^*,9R^*)-3-formamido-1(10)-cadinene], and an amine [(−)-halichamine] functionality were isolated from the Thai marine sponge Halichondria sp., together with two steroids, ergosterol and ergosterol peroxide. (−)-Axisonitrile-3 was isolated from the natural source for the first time, while (+)-axamide-3 and (−)-halichamine were new metabolites. The structures of these compounds were elucidated on the basis of their spectroscopic data and by chemical transformations. All sesquiterpenes were tested for their cytotoxic activity against six cancer cell lines (HeLa, HuCCA-1, A549, MOLT-3, HepG2, MDA-MB231). Only (−)-axisonitrile-3 showed strong activity to the HepG2 cell line with an IC₅₀ value of 1.3 μM.     

Coelodiol and coeloic acid, ent-isocopalane diterpenes from the Indonesian sponge Coelocarteria cfr. singaporensis

Two novel ent-isocopalane diterpenes, coelodiol (1) and coeloic acid (2), the latter characterized by an unique oxidative degradation of ring A, have been isolated from the Indonesian sponge Coelocarteria cfr. singaporensis. The stereostructure of these metabolites has been established through interpretation of NMR data and application of the exciton chirality CD method. Coelodiol (1) and coeloic acids (2) were found to inhibit the growth of MKN-45 cell line (human gastric adenocarcinoma).     

Stelliferins J-N, isomalabaricane-type triterpenoids from Okinawan marine sponge Rhabdastrella cf. globostellata

Five new isomalabaricane-type triterpenoids, stelliferins J-N (1-5), were isolated from Okinawan marine sponge Rhabdastrella cf. globostellata. The structures of 1-5 were elucidated from the spectroscopic data and chemical means including application of a modified Mosher’s method and an exciton chirality method.     

Plakoridine C, a novel piperidine alkaloid from an Okinawan marine sponge Plakortis sp.

A new piperidine alkaloid plakoridine C (1) has been isolated from an Okinawan marine sponge Plakortis species, and the structure was elucidated from spectroscopic data. Plakoridine C (1) is a new alkaloid possessing a piperidine ring connected to a β-keto-γ-lactone through a double bond.     

Synthetic approaches towards an indole alkaloid isolated from the marine sponge Halichondria melanodocia

The exocyclic analogue of the indole alkaloid isolated from the marine sponge Halichondria melanodocia has been prepared via olefination of a phosphonoester derived from 3-(2-bromoacyl)indole. The formation of an unexpected indolylazepine is also discussed.     

Chloroscabrolides, chlorinated norcembranoids from the Indonesian soft coral Sinularia sp.

Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded two known and three new C-4 norcembranoids, named chloroscabrolides A (3) and B (4) and prescabrolide (5). Chloroscabrolide A is a pentacyclic norcembranoid including an unprecedented THF-type ring to connect C-13 and C-15; furthermore, it is only the second chlorinated cembranoid derivative to be reported in the literature. The relative configuration of chloroscabrolide A has been established on the basis of a comparison between experimental ¹³C NMR data and DFT-calculated ¹³C NMR chemical shifts. All the isolated norcembranoids have been evaluated for iNOS protein inhibition.     

Euryjanicin A: a new cycloheptapeptide from the Caribbean marine sponge Prosuberites laughlini

A new proline-containing cycloheptapeptide, euryjanicin A (1), has been isolated from the marine sponge Prosuberites laughlini indigenous to Puerto Rico, and its structure established by an X-ray crystal structure determination. The absolute configuration of each amino acid residue was determined by Marfey’s method.     

Cytosporones O, P and Q from an endophytic Cytospora sp.

Cytosporones O, P and Q, together with the known compounds cytosporones B, C, D, E and dothiorelones A, B, C, and H were isolated from the ascomycete fungus Cytospora sp. during a chemotaxonomic study of fungal endophytes belonging to the related genera Cytospora and Phomopsis from Brazil. The structures were determined by NMR spectroscopy and mass spectrometry. With exception of cytosporones D, E, Q, and dothiorelone B, all compounds were consistently detected in the metabolite profiles of eight Cytospora isolates investigated; and were also produced by a distinct chemotype of Phomopsis.     

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.     

Jaspolides G and H, unique bisisomalabaricanes from the Chinese marine sponge Jaspis sp.

Two unique bisisomalabaricanes jaspolides G (1) and H (2) were isolated from the marine sponge Jaspis sp. Their structures were elucidated on the basis of extensive spectroscopic data (IR, MS, and 1D and 2D NMR) analyses. A possible biogenetic pathway via Diels-Alder dimerization for jaspolides G and H was also proposed.     

Dactylospongiaquinone, a new meroterpenoid from the Australian marine sponge Dactylospongia n. sp.

Chemical investigation of the sponge Dactylospongia n. sp. collected near Mooloolaba, S.E. Queensland, has led to the isolation of dactylospongiaquinone (7) together with the known quinones (2-5). The new metabolite 7 possesses a different carbon framework from the known dictyoceratidaquinone (9) and is suggested to possess a cis-fused ring junction by extensive NOESY studies combined with molecular modelling calculations. The relative stereochemistry of the previously described cyclospongiaquinone-1 (3) and dehydrocyclospongiaquinone-1 (4) is also assigned on the basis of NOESY analyses. Full NMR spectroscopic assignments are provided for all compounds.     

Exiguolide, a new macrolide from the marine sponge Geodia exigua

A new 20-membered macrolide designated exiguolide has been isolated from the marine sponge Geodia exigua, and its structure determined by interpretation of spectroscopic data. Exiguolide specifically inhibited fertilization of sea urchin (Hemicentrotus pulcherrimus) gametes but not embryogenesis of the fertilized egg.     

New bioactive cyclic peroxides from the Caribbean marine sponge Plakortis zyggompha

The new plakortide Q (1) has been isolated from the little studied marine sponge Plakortis zyggompha, together with the six new cyclic peroxide analogues 2-7 in their methyl ester forms 2a-7a. Their structure was fully elucidated through NMR and MS analyses and the relative stereochemistry of the 1,2-dioxane ring was established after interpretation of the coupling constant values and the NOESY data. The carboxylic acid function of these compounds was proved to be very reactive and methylation was found to take place during the purification process. The non-esterified peroxides exhibited more cytotoxic activity against human tumor cell lines than their corresponding methyl esters.