The addition of CaBr(2) to the fermentation of a marine-derived Fusarium tricinctum resulted in production of halogenated chlamydosporol analogues. Two new antimicrobial halogenated pyranopyranones, bromomethylchlamydosporols A (1) and B (2), and two known compounds, chlamydosporol (an inseparable epimeric mixture of 7R:7S = 1:1 from (1)H NMR data) (3) and fusarielin A (4), were isolated from the culture. The structures of 1 and 2 were assigned through a combination of spectroscopic data analyses. Compounds 1-4 exhibited mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain were as follows: compounds 1 and 2 showed an MIC of 15.6 μg/mL against S. aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus, and compounds 3 and 4 exhibited an MIC of 31.5 μg/mL against S. aureus and methicillin-resistant S. aureus and 62.5 μg/mL against multidrug-resistant S. aureus.

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Marine-derived microorganisms continue to attract attention as a rich source of structurally novel bioactive metabolites that are potential lead compounds for the development of new drugs. 1,2 When the marine-derived microorganisms were cultured under saline condition, they rarely produced interesting biological halogenated metabolites (for example, salinosporamide A 3 of a highly potent inhibitor of the 20S proteasome and its halogenated derivatives, 4 cytotoxic halogenated polyenyl pyrroles, isorumbrin and bromoisorumbrin, 5 nematicidal and antimicrobial lachnumon and mycorrhizin A derivatives, 6 bromomyrothenone B, 7 and antibacterial chlorohydroaspyrones A and B 8 ). Encouraged by the detection of halogenated marine analogs, we manipulated the fermentation of Phoma herbarum by the addition of halide salts in an effort to gain access to a wider cross-section of halogenated secondary metabolites. This report describes the production, isolation, and identification of halogenated benzoquinones (1, 2), as well as the radical-scavenging activity of these compounds.The fungal strain, P. herbarum, was isolated from the edible marine red alga Gloiopeitis tenax (Korean Name: ChamGasari) collected in Cheokpo, Tongnyeong, Korea and identified based on 18S rRNA analyses (SolGent, Daejeon, Korea), identity of 99%. A voucher specimen is deposited at Pukyong National University with the code MFA301. The fungus was cultured (1 literÂ10) in SWS medium consisting of soytone (0.1%), soluble starch (1.0%) and seawater (100%). The cultures were incubated at 29 1C for 10 days on a rotary shaker (120 r.p.m.), and CaBr 2 (50 mM) 6,9 was subsequently added. Incubation was further continued for 10 days under the same condition. The culture control was incubated in the absence of CaBr 2 in the same manner as described above.The mycelium and broth were separated by filtration using cheesecloth. The broth was extracted with EtOAc to afford a crude extract (0.8 g). The extract was subjected to silica gel flash chromatography. Elution was performed with n-hexane-EtOAc (stepwise, 0-100% EtOAc) to yield five fractions. Fraction 2, which was active in 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay, was separated by medium-pressure liquid chromatography (ODS-A; YMC Co. Ltd, Kyoto, Japan) using an H 2 O-MeOH gradient elution to afford crude compounds 1 and 2. These were further purified by HPLC (ODS-A, 10Â250 mm, 1 ml min À1 ; YMC Co. Ltd) using a 30-min gradient program of 50-100% MeOH in H 2 O to furnish 1 (6.5 mg) and 2 (6.0 mg). Compounds 3 (15 mg) and 4 (5.0 mg) were isolated from fraction 3 by the same chromatographic method as described above.Bromochlorogentisylquinone A (1): a yellow solid; IR (KBr) n max 3399, 3064, 2927, 2853, 1670, 1588, 1428, 1316, 1269, 1232, 1204, 1103, 1025, 941, 876, 803 Table 1 for NMR spectral data.Bromochlorogentisylquinone B (2): a yellow solid, IR (KBr) n max 3401, 3058, 2921, 1673, 1587, 1316, 1232, 1103, 1025, 941, 875 Table 1 for NMR spectral data.Chlorogentisyl alcohol (3) and gentisyl a...

Manipulation of the fermentation of the marine-derived fungus Penicillium chrysogenum by addition of CaBr(2) resulted in induced production of bromodiphenyl ether analogs. Two new free-radical-scavenging polybrominated diphenyl ethers, 1 and 2, and three known diphenyl ethers, 3,3'-dihydroxy-5,5'-dimethyldiphenyl ether (3), and an inseparable mixture of violacerol-I (4) and violacerol-II (5) were isolated. The structures of the two new polybromodiphenyl ethers 1 and 2 were assigned by combined spectroscopic-data analysis, including deuterium-induced isotope effect. Compounds 1-3, and a mixture of 4 and 5 exhibited radical-scavenging activities against 1,1-diphenyl-2-picrylhydrazyl with IC(50) values of 18, 15, 42, and 6 μM, respectively. With the exception of 3, the compounds were, therefore, more active than the positive control, ascorbic acid (IC(50) 20 μM).