Rugulotrosins A and B: Two new antibacterial metabolites from an Australian isolate of a Penicillium sp

Two new antibacterial agents, rugulotrosin A (1) and B (2), were obtained from cultures of a Penicillium sp. isolated from soil samples acquired near Sussex Inlet, New South Wales, Australia. Rugulotrosin A (1) is a chiral symmetric dimer, and its relative stereostructure was determined by spectroscopic and X-ray crystallographic analysis. Rugulotrosin B (2) is a chiral asymmetric dimer isomeric with 1. Its structure was determined by spectroscopic analysis with comparison to the co-metabolite 1 and previously reported fungal metabolites. Both rugulotrosins A and B displayed significant antibacterial activity against Bacillus subtilis, while rugulotrosin A was also strongly active against Enterococcus faecalis and B. cereus.     

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.     

Use of experimental design for the optimization of the production of new secondary metabolites by two Penicillium species

A fractional factorial design approach has been used to enhance secondary metabolite production by two Penicillium strains. The method was initially used to improve the production of bioactive extracts as a whole and subsequently to optimize the production of particular bioactive metabolites. Enhancements of over 500% in secondary metabolite production were observed for both P. oxalicum and P. citrinum. Two new alkaloids, citrinalins A (5) and B (6), were isolated and identified from P. citrinum cultures optimized for production of minor metabolites.     

Sculezonones A and B, two metabolites possessing a phenalenone skeleton from a marine-derived fungus Penicillium species

Two new metabolites possessing a phenalenone skeleton, sculezonones A (1) and B (2), were isolated from cultured broth of the fungus Penicillium sp., which was separated from the Okinawan marine bivalve Mytilus coruscus, and the structures were elucidated by spectroscopic data.     

Citromycetins and bilains A-C: new aromatic polyketides and diketopiperazines from Australian marine-derived and terrestrial Penicillium spp

Chemical analysis of an Australian marine-derived isolate of Penicillium bilaii, collected from the Huon estuary, Port Huon, Tasmania, yielded the known fungal aromatic polyketides citromycetin (1) and citromycin (2) together with two dihydro analogues, (-)-2,3-dihydrocitromycetin (3) and (-)-2,3-dihydrocitromycin (4). An Australian terrestrial isolate of Penicillium striatisporum collected near Shalvey, New South Wales, also yielded citromycetin (1), citromycin (2), and the new dihydro analogue (-)-2,3-dihydrocitromycetin (3), together with fulvic acid (5), anhydrofulvic acid (6), and a selection of new methoxylated analogues, 12-methoxycitromycetin (7), 12-methoxycitromycin (8), (-)-12-methoxy-2,3-dihydrocitromycetin (9), and 12-methoxyanhydrofulvic acid (10). P. bilaii also yielded the rare siderophore pistillarin (11), the known diketopiperazines cyclo-(L-Phe -L-Pro) (12), cyclo-(L-Pro-L-Tyr) (13), cyclo-(L-Pro-L-Val) (14), and cis-bis(methylthio)silvatin (15), and three new diketopiperazines, bilains A-C (16-18). The structures for the Penicillium metabolites 1- 18 were assigned by a combination of detailed spectroscopic analysis, including correlation with relevant literature data, chemical derivatization, degradation, and biosynthetic considerations. The citromycin polyketides 2 and 4 and the diketopiperazine 15 were weakly cytotoxic.     

Spongiadioxins A and B, two new polybrominated dibenzo-p-dioxins from an Australian marine sponge Dysidea dendyi.

Two new cytotoxic tetrabromodibenzo-p-dioxins, spongiadioxins A (1) and B (2), were isolated from an Australian marine sponge Dysidea dendyi. The structures of these compounds were established by 1D and 2D NMR spectroscopy, X-ray analysis of the methyl ether of spongiadioxin A (3), and synthesis of the methyl ether of spongiadioxin B (4) from diphenyl ether (9) isolated from Dysidea herbacea.     

Antifungal and antibacterial metabolites from a sclerotium-colonizing isolate of Mortierella vinacea

The known compound methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (1) and three new related metabolites, which we have named mortivinacins A (2), B (3), and C (4), were identified as metabolites of the fungus Mortierella vinacea. Nicotinic acid (5) was also encountered. This isolate of M. vinacea was obtained from an Aspergillus flavus sclerotium during field studies of sclerotium longevity in soil. Compounds 1-5 were isolated by chromatographic fractionation of organic extracts from M. vinacea solid-substrate fermentation cultures, and the structures were assigned by analysis of NMR and MS data. Compounds 1, 2, and 5 were responsible for the antibacterial and antifungal activities of the extract.     

Gymnoascolides A-C: aromatic butenolides from an Australian isolate of the soil ascomycete Gymnoascus reessii

Three new aromatic butenolides, gymnoascolides A-C (1-3), have been isolated from the Australian soil ascomycete Gymnoascus reessii and assigned structures on the basis of detailed spectroscopic analysis. The absolute configurations of gymnoascolides B (2) and C (3) at C-5 were solved using a combination of chemical derivatization and quantum chemical simulations.     

Blanchaquinone: a new anthraquinone from an Australian Streptomyces sp

Chemical analysis of an Australian Streptomyces species yielded a range of known anthracyclines and biosynthetically related metabolites, including daunomycin (1), epsilon-rhodomycinone (2), 11-hydroxyauramycinone (3), 11-hydroxysulfurmycinone (4), aklavinone (5), bisanhydro-gamma-rhodomycinone (6), and the anthraquinone 7, as well as the hitherto unreported blanchaquinone (8). The structure assigned to 8 was secured by detailed spectroscopic analysis and correlation to known analogues, such as the anthraquinone 7. This account also represents the first natural occurrence of 3, 4, and 7 and the first spectroscopic characterization of 11-hydroxysulfurmycinone (4).     

Penifulvins B-E and a silphinene analogue: sesquiterpenoids from a fungicolous isolate of Penicillium griseofulvum

Penifulvins B-E (2-5), four new sesquiterpenoids with a dioxa[5.5.5.6]fenestrane ring system, have been isolated from cultures of an isolate of Penicillium griseofulvum (NRRL 35584), together with a new silphinene derivative, 12-hydroxysilphinene-15-oic acid (6). Penifulvins B-E (2-5) are oxidized analogues of penifulvin A (1) and were identified by analysis of NMR and MS data. 12-Hydroxysilphinen-15-oic acid (6) is biogenetically similar, and penifulvins A-E are presumed to be derived from a silphinene precursor. The structures of 2-6, including absolute configuration, were assigned by analysis of NMR data and application of chemical methods.     

Auranticins A and B: two new depsidones from a mangrove isolate of the fungus Preussia aurantiaca

Auranticins A and B, two new antimicrobial depsidones, have been obtained from a mangrove isolate of the fungus Preussia aurantiaca. The structures were determined through analysis of selective INEPT, decoupling, COSY, and NOESY experiments.     

Lorneamides A and B: two new aromatic amides from a southern Australian marine actinomycete

A marine actinomycete (MST-MA190) isolated from a sample of beach sand collected near Lorne on the southwest coast of Victoria, Australia, has yielded two new aromatic amides, lorneamide A (1) and lorneamide B (2). The lorneamides belong to a novel class of tri-alkyl-substituted benzenes, and their structures were determined by spectroscopic methods.     

New bioactive metabolites from a freshwater isolate of the fungus Kirschsteiniothelia sp.

The new cytotoxic naphthoquinone dimer kirschsteinin [5], two new chlorinated diphenyl ethers 8 and 9, three known naphthoquinone derivatives 1, 2, and 7, a monoacetyl derivative of 2, and the (-)-enantiomer of O-methylasparvenone [4], have been isolated from a previously undescribed species of Kirschsteiniothelia. The structures of these compounds were assigned primarily by nmr studies and by spectral comparisons.     

Thiersindoles A-C: new indole diterpenoids from Penicillium thiersii

Three new 3-substituted indole diterpenoids (thiersindoles A-C; 1-3) have been isolated from organic extracts of a new Penicillium species (P. thiersii). Their structures, including absolute stereochemistry, were determined by analysis of NMR data and application of Mosher's method. Thiersindoles A-C are biogenetically related to the aflavinines, although the [6,6,5] tricyclic diterpenoid skeleton in compounds 1 and 2 is unprecedented in any of the known members of this class.     

Bioactive diterpenoids, a new jatrophane and two ent-abietanes, and other constituents from Euphorbia pubescens

A new jatrophane diterpene, pubescenol (1), known ent-abietane lactones, helioscopinolide A (2) and B (3), and taraxerone, 24-methylenecycloartanol, and vanillin have been isolated from Euphorbia pubescens. Diterpenes 1-3 and previously described pubescene D (4) were shown to be moderate inhibitors of the growth of MCF-7, NCI-H460, and SF-268 human tumor cell lines, whereas compounds 2 and 3 also exhibited significant antibacterial activity against Staphylococcus aureus.     

Cyclotheonamide E4 and E5, new potent tryptase inhibitors from an Ircinia species of sponge

Tryptase is a protease released from mast cells and is believed to contribute to the inflammatory process in allergic diseases including asthma. In the course of screening to find tryptase inhibitors, we isolated two new tryptase inhibitors, cyclotheonamide E4 (3) and E5 (4), from a marine sponge of the genus Ircinia. The structures of these molecules were determined by interpretation of 1H and 13C NMR spectra, and they were shown to be closely related to the previously reported cyclotheonamides E (1), E2, and E3 (2). These molecules contain two unusual amino acids, vinylogous tyrosine and alpha-ketohomoarginine, which are involved in strong activities against serine proteases. Cyclotheonamide E4 showed potent inhibitory activity against human tryptase (IC50 5.1 nM). Therefore, cyclotheonamide E4 may be useful as a therapeutic agent in the treatment of allergic diseases including asthma.     

Dictyosphaeric acids A and B: new decalactones from an undescribed Penicillium sp. obtained from the alga Dictyosphaeria versluyii

Fungal isolate F01V25 was obtained from the alga Dictyosphaeria versluyii collected near Dravuni, Fiji, in 2001 and represented a previously undescribed Penicillium sp. Fermentation of isolate F01V25 resulted in the production of two new polyketides, dictyosphaeric acids A and B, along with the known anthraquinone carviolin. The relative stereochemistry of dictyosphaeric acids A and B was determined using the J-based configuration analysis method in conjunction with ROE and NOE correlations.     

Georgamide, a new cyclic depsipeptide with an alkynoic acid residue from an Australian cyanobacterium.

A cyclic depsipeptide, georgamide (1), was isolated from an Australian cyanobacterium and characterized by spectroscopic means. The constituent units were five amino acid residues, one each of L-Thr, L-Pro, L-Val, N-Me-L-Val, and N-Me-L-Phe, and two hydroxy carboxylic acids, 2(S)-hydroxy-3(R)-methylpentanoic acid and the unusual 2,2-dimethyl-3-hydroxy-7-octynoic acid. The stereochemistry was determined by hydrolysis of the peptide followed by derivatization and HPLC comparison with standard samples.     

New diterpene glycosides of the fungus Acremonium striatisporum isolated from a sea cucumber

Three new diterpene glycosides, virescenosides O (1), P (2), and Q (3), have been isolated from a marine strain of Acremonium striatisporum KMM 4401 associated with the holothurian Eupentacta fraudatrix. Their structures were determined on the basis of HRMALDIMS and NMR data as beta-D-altropyranosido-19-isopimara-8(14),15-diene-7alpha,3beta-diol (1), beta-D-altropyranosido-19-7-oxoisopimara-8(9),15-diene-3beta-ol (2), and beta-D-mannopyranosido-19-isopimara-7,15-diene-3beta-ol (3). The cytotoxic activity of the virescenosides was examined.     

14'-Hydroxymytoxin B and 16-hydroxyroridin E,two new cytotoxic trichothecenes from Myrothecium roridum

Two new trichothecenes, 14'-hydroxymytoxin B (1) and 16-hydroxyroridin E (3), were isolated from a fermentation extract of Myrothecium roridum. The structures of 1 and 3 were determined by spectral data interpretation. Both compounds showed potent cytotoxic activity against primary soft-tissue sarcoma cells.