Calbistrin E and two other new metabolites from an Australian isolate of Penicillium striatisporum

An Australian isolate of Penicillium striatisporum collected near Shalvey, New South Wales, exhibited selective antifungal activity against Candida albicans versus Saccharomyces cerevisiae. Bioassay-directed fractionation yielded members of the rare class of fungal metabolites known as the calbistrins. These included a new example of this structure class, calbistrin E (1), as well as the known polyenes calbistrin C (2) and deformylcalbistrin A (3). Also recovered from P. striatisporum were new triene and butenolide acids, striatisporin A (4) and striatisporolide A (5), together with the known fungal metabolites versiol (6) and (+)-hexylitaconic acid (7). Structures for all metabolites were determined by detailed spectroscopic analysis.

Spongosoritin A: A new polyketide from a Fijian marine sponge, Spongosorites sp.

A new polyketide, spongosoritin A, with a rare vinylagous alpha,beta-unsaturated gamma-lactone moiety was isolated from a Fijian marine sponge, Spongosorites sp., and the structure assigned by detailed spectroscopic analysis.

Aspergillazines A-E: novel heterocyclic dipeptides from an Australian strain of Aspergillus unilateralis

Biological and chemical pro ling of an Australian strain of the fungus Aspergillus unilateralis (MST-F8675), isolated from a soil sample collected near Mount Isa, Queensland, revealed a complex array of metabolites displaying broad chemotherapeutic properties. Noteworthy among these metabolites were a unique series of highly modified dipeptides aspergillazines A-E, incorporating a selection of unprecedented and yet biosynthetically related heterocyclic systems. Co-occurring with the aspergillazines was the recently described marine-derived fungal metabolite trichodermamide A (cf. penicillazine), whereas re-fermentation of A. unilateralis in NaCl (1%) enriched media resulted in co-production of the only other known example of this structure class, the marine-derived fungal metabolite trichodermamide B. Further investigation of A. unilateralis returned the known terrestrial fungal metabolite viridicatumtoxin as the cytotoxic and antibacterial principle, together with E-2-decenedioic acid, ferulic acid, (7E,7'E)-5,5'-diferulic acid and (7E,7'E)-8,5'-diferulic acid. The aromatic diacids have previously been reported from the chemical and enzymatic (esterase) treatment of plant cell wall material, with their isolation from A. unilateralis being their first apparent reported occurrence as natural products. Structures for all metabolites were determined by detailed spectroscopic analysis and, where appropriate, comparison to literature data and/or authentic samples.

The fate of Lyngbya majuscula toxins in three potential consumers

Blooms of Lyngbya majuscula have been reported with increasing frequency and severity in the last decade in Moreton Bay, Australia. A number of grazers have been observed feeding upon this toxic cyanobacterium. Differences in sequestration of toxic compounds from L. majuscula were investigated in two anaspideans, Stylocheilus striatus, Bursatella leachii, and the cephalaspidean Diniatys dentifer. Species fed a monospecific diet of L. majuscula had different toxin distribution in their tissues and excretions. A high concentration of lyngbyatoxin-a was observed in the body of S. striatus (3.94 mg/kg(-1)) compared to bodily secretions (ink 0.12 mg/kg- 1; fecal matter 0.56 mg/kg(-1); eggs 0.05 mg/kg(-1)). In contrast, B. leachii secreted greater concentrations of lyngbyatoxin-a (ink 5.41 mg/kg(-1); fecal matter 6.71 mg/kg(-1)) than that stored in the body (2.24 mg/kg(-1)). The major internal repository of lyngbyatoxin-a and debromoaplysiatoxin was the digestive gland for both S. striatus (6.31 +/- 0.31 mg/kg(-1)) and B. leachii (156.39 +/- 46.92 mg/kg(-1)). D. dentifer showed high variability in the distribution of sequestered compounds. Lyngbyatoxin-a was detected in the digestive gland (3.56 +/- 3.56 mg/kg(-1)) but not in the head and foot, while debromoaplysiatoxin was detected in the head and foot (133.73 +/- 129.82 mg/kg(-1)) but not in the digestive gland. The concentrations of sequestered secondary metabolites in these animals did not correspond to the concentrations found in L. majuscula used as food for these experiments, suggesting it may have been from previous dietary exposure. Trophic transfer of debromoaplysiatoxin from L. majuscula into S. striatus is well established; however, a lack of knowledge exists for other grazers. The high levels of secondary metabolites observed in both the anaspidean and the cephalapsidean species suggest that these toxins may bioaccumulate through marine food chains.

Roquefortine E, a diketopiperazine from an Australian isolate of Gymnoascus reessii

The new isoprenylated diketopiperazine roquefortine E (6) has been isolated from an Australian soil isolate of the ascomycete Gymnoascus reessii. The known fungal metabolite roquefortine C (1) was also recovered as the major antibacterial principle, and all structures were assigned by detailed spectroscopic analysis.

A galloylated cyanogenic glycoside from the Australian endemic rainforest tree Elaeocarpus sericopetalus (Elaeocarpaceae)

A cyanogenic glycoside -6'-O-galloylsambunigrin - has been isolated from the foliage of the Australian tropical rainforest tree species Elaeocarpus sericopetalus F. Muell. (Elaeocarpaceae). This is the first formal characterisation of a cyanogenic constituent in the Elaeocarpaceae family, and only the second in the order Malvales. 6'-O-galloylsambunigrin was identified as the principal glycoside, accounting for 91% of total cyanogen in a leaf methanol extract. Preliminary analyses indicated that the remaining cyanogen content may comprise small quantities of sambunigrin, as well as di- and tri-gallates of sambunigrin. E. sericopetalus was found to have foliar concentrations of cyanogenic glycosides among the highest reported for tree leaves, up to 5.2 mg CN g(-1) dry wt. (c) 2006 Elsevier Ltd. All rights reserved.

Feeding preference and deterrence in rabbitfish Siganus fuscescens for the cyanobacterium Lyngbya majuscula in Moreton Bay, south-east Queensland, Australia

Rabbitfish Siganus fuscescens preferences for Lyngbya majuscula collected from three bloom locations in Moreton Bay, Queensland, Australia, were tested along with a range of local plant species in the laboratory. Consumption of L. majuscula by fish did not differ between wild and captive-bred fish (P = 0.152) but did differ between bloom location (P = 0.039). No relationship was found between consumption rates and lyngbyatoxin-a concentration (r(2) = 0.035, P = 0.814). No correlation existed between C : N and proportion of food consumed when all food types were analysed statistically, whereas a clear correlation was observed when L. majuscula was removed from the calculations. In simulated bloom conditions, fish avoided ingestion of L. majuscula by feeding through gaps in the L. majuscula coverage. Both wild and captive-bred S. fuscescens showed a distinct feeding pattern in 10 day no-choice feeding assays, with less L. majuscula being consumed than the preferred red alga Acanthophora spicifera. Lyngbya majuscula however, was consumed in equal quantities to A. spicifera by wild S. fuscescens when lyngbyatoxin-a was not detectable. Wild fish probably do not preferentially feed on L. majuscula when secondary metabolites are present and are not severely impacted by large L. majuscula blooms in Moreton Bay. Furthermore, poor feeding performance in both captive-bred and wild S. fuscescens suggests that they would exert little pressure as a top-down control agent of toxic L. majuscula blooms within Moreton Bay. (c) 2006 The Fisheries Society of the British Isles.

Isokibdelones: Novel heterocyclic polyketides from a Kibdelosporangium sp.

The isokibdelones are an unprecedented family of polyketides produced by an Australian isolate of a rare actinomycete, Kibdelosporangium sp. The structures of the isokibdelones were assigned by spectroscopic analysis and chemical interconversion. A proposed biosynthesis requires a novel molecular twist that generates an unprecedented heterocyclic system and differentiates the isokibdelones from their kibdelone co-metabolites. SAR analysis on the isokibdelones further defines the anticancer pharmacophore of these novel polyketides.

Polyenylpyrroles and polyenylfurans from an Australian isolate of the soil ascomycete Gymnoascus reessii

An Australian isolate of the soil ascomycete Gymnoascus reessii yielded a series of cytotoxic metabolites, including the known polyenylpyrroles rumbrin (1) and auxarconjugatin A (2), and the new rumbrin stereoisomer 12E-isorumbrin (3), as well as an unprecedented class of polyenylfurans exemplified by gymnoconjugatins A (4) and B (5). Structures were assigned with detailed spectroscopic analysis.

Quinolactacins revisited: from lactams to imide and beyond

Chemical analysis of a solid phase fermentation of an Australian Penicillium citrinum strain has returned all known examples of a rare class of N-methyl quinolone lactams, quinolactacins A2 (1), B2 (2), C2 (3) and Al (4), together with the new quinolactacins B1 (5), C1 (6), D1 (7) and D2 (8), and the novel derivatives quinolonimide (9) and quinolonic acid (10). Complete stereostructures were assigned to all these compounds by detailed spectroscopic analysis and chemical interconversion. Carefully controlled and monitored decomposition studies have confirmed that quinolactacins readily undergo C-3 epimerization and oxidation, and under appropriate conditions convert to quinolonimide and quinolonic acid. Mechanisms for key transformations are proposed. The decomposition studies suggested that only quinolactacins A2 (1) and B2 (2) are genuine natural products, with all other isolated compounds being decomposition artefacts. Quinolactacins C1 (6), C2 (3), and the racemic mixture of quinolactacins D1/D2 (8/7) all displayed notable cytotoxic activity.

Mooloolabenes A-E, norsesterterpenes from the Australian sponge Hyattella intestinalis

Five new norsesterterpenes, mooloolabenes A-E (1-5), and the new sesterterpene mooloolaldehyde (6), related to the scalarane family of compounds, were isolated from an acetone extract of the Australian sponge Hyattella intestinalis. Structural elucidation, including relative stereochemical assignment, was based on spectroscopic analysis. All compounds tested showed cytotoxic activity against the P388 cell line.

Dietary selectivity for the toxic cyanobacterium Lyngbya majuscula and resultant growth rates in two species of opisthobranch mollusc

Trophodynamics of blooms of the toxic marine cyanobacterium Lyngkya majuscula were investigated to determine dietary specificity in two putative grazers: the opisthobranch molluscs, Stylocheilus striatus and Bursatella leachii. S. striatus is associated with L. majuscula blooms and is known to sequester L. majuscula metabolites. The dietary specificity and toxicodynamics of B. leachii in relation to L. majuscula is less well documented. In this study we found diet history had no significant effect upon dietary selectivity of S. striatus when offered a range of plant species. However, L. majuscula chemotype may alter S. striatus' selectivity for this cyanobacterium. Daily biomass increases between small and large size groups of both species were recorded in no-choice consumption trials using L. majuscula. Both S. striatus and B. leachii preferentially consumed L. majuscula containing lyngbyatoxin-a. Increase in mass over a 10-day period in B. leachii (915%) was significantly greater than S. striatus (150%), yet S. striatus consumed greater quantities of L. majuscula (g day(-1)) and thus had a lower conversion efficiency (0.038) than B. leachii (0.081) based on sea hare weight per gram of L. majuscula consumed day(-1). Our findings suggest that growth rates and conversion efficiencies may be influenced by sea hare maximum growth potential, acquisition of secondary metabolites or diet type. (C) 2005 Elsevier B.V. All rights reserved.

Synthesis of 'difficult' peptides free of aspartimide and related products, using peptoid methodology

We developed an efficient, cost effective strategy for Fmoc-based solid phase synthesis of 'difficult' peptides and/or peptides containing Asp/Asn-Gly sequences, free of aspartimide and related products, using a peptoid methodology for the preparation of N-substituted glycines.