berkeleytrione and berkeleydione

A 13-step total synthesis of the fungal meroterpenoid berkeleyone A is reported. The molecular skeleton is formed using the first examples of two critical construction reactions: (1) an epoxide-initiated, β-ketoester-terminated polycyclization, and (2) an isomerization-cyclization cascade to generate the remaining bicyclo[3.3.1]nonane framework. The resulting 6-step synthesis of the carbocyclic core of the berkeleyone natural products has been used to access protoaustinoid A and berkeleyone A, and will aid future biosynthetic investigations into the origin of related natural products.

Topics: Macrolides; Molecular Conformation; Stereoisomerism; Terpenes

The Berkeley Pit, an acid mine waste lake, is a source of extremophilic microorganisms that produce interesting bioactive compounds. We have previously reported the isolation of berkeleydione (1), berkeleytrione (2), the berkeleyacetals, and the berkeleyamides from the Pit Lake fungus Penicillium rubrum. In this paper we report the isolation and characterization of berkeleyones A-C (4, 5, and 7) as well as previously described preaustinoid A (3) and A1(6) from this same fungus. These compounds were evaluated as inhibitors of the signaling enzyme caspase-1 and as potential inhibitors of interleukin 1-β production by inflammasomes in induced THP-1 cell line assays.

Topics: Caspase Inhibitors; Humans; Inflammasomes; Interleukin-1beta; Lakes; Macrolides; Monocytes; Penicillium; Terpenes

Three novel hybrid polyketide-terpenoid metabolites were isolated from a Penicillium minioluteum strain. Their structures were determined by NMR spectroscopic analyses and X-ray crystallography. The proposed biosynthetic pathway including a unique retro-Claisen migration of methyl carbonate correlates the three compounds with berkeleydione and berkeleytrione.

Topics: Crystallography, X-Ray; Macrolides; Methicillin Resistance; Microbial Sensitivity Tests; Models, Molecular; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Penicillium; Staphylococcus aureus; Terpenes

Berkeley Pit Lake is a 1500 ft deep abandoned open-pit copper mine filled with over 1140 billion liters of acidic, metal-sulfate-contaminated water. This harsh environment is proving to be a source of unusual microorganisms that produce novel bioactive compounds. We recently reported the structures of berkeleydione (1) and berkeleytrione (2), two novel hybrid polyketide-terpenoid metabolites isolated from a deep water Penicillium sp. growing in Berkeley Pit Lake. In this paper we report the structures of three new compounds, berkeleyacetals A-C ( 3-5) isolated from extracts of this fungus. The structures of these compounds were deduced by comparison of mass spectral and NMR data to that of berkeleydione (1).

Topics: Acids; Macrolides; Nuclear Magnetic Resonance, Biomolecular; Penicillium; Terpenes; Waste Products; Water

[structure: see text] Two novel hybrid polyketide-terpenoid metabolites were isolated from a Penicillium sp. growing in the Berkeley Pit Lake of Butte, Montana. Their structures were deduced by spectroscopic analysis and confirmed by single-crystal X-ray analysis on berkeleydione (1). Both compounds inhibited matrix metalloproteinase-3 and caspase-1, and berkeleydione showed activity toward non-small-cell lung cancer in NCI's human cell line antitumor screen.

Topics: Acids; Caspase Inhibitors; Cell Line, Tumor; Crystallography, X-Ray; Drug Evaluation, Preclinical; Enzyme Inhibitors; Fresh Water; Humans; Macrolides; Magnetic Resonance Spectroscopy; Matrix Metalloproteinase Inhibitors; Mining; Molecular Structure; Montana; Penicillium chrysogenum; Terpenes