oxepins and pterulone

An efficient synthesis of the three halogenated naturally occurring products, pterulone (2), pterulone B (3) and alcohol 5, and of a wide range of related unnatural analogues has been achieved starting from the two readily available 1-benzoxepine sulfonyl-containing intermediates 6a and 6b. The biological activities of pterulone and some of the synthesized analogues were tested against a wide spectrum of phytopathogenic fungi.

Topics: Alcohols; Alkylation; Antifungal Agents; Benzofurans; Fungi; Molecular Structure; Oxepins; Phenol; Structure-Activity Relationship

Pterulinic acid (1) and pterulone (2), two novel halogenated antibiotics, were isolated from fermentations of Pterula sp. 82168. Both compounds exhibited significant antifungal and weak or no cytotoxic activities. 1 and 2 are effective inhibitors of eucaryotic respiration. The target of the antibiotics resides within the mitochondrial NADH:ubiquinone oxidoreductase (complex I).

Topics: Acetates; Animals; Antifungal Agents; Benzofurans; Cattle; Chromatography, High Pressure Liquid; Electron Transport Complex I; Fermentation; Microbial Sensitivity Tests; Mitochondria; NADH, NADPH Oxidoreductases; Oxepins; Oxygen Consumption; Stereoisomerism; Tumor Cells, Cultured

The structures of two novel fungal antibiotics, isolated from a Pterula species, that interfere with the NADH:ubiquinone oxidoreductase and inhibit the respiration of eucaryotes, were determined by spectroscopic techniques. Both compounds, pterulinic acid (1a) and pterulone (2), contain a 1-benzoxepin ring system and are chlorinated. Pterulinic acid (1a), which was obtained as a 1:5 inseparable mixture of the two isomers (Z)-1a and (E)-1a, in addition contains a furan. Their structures were determined by mass spectrometry and NMR spectroscopy, and 2D heteronuclear correlation experiments permitted the assignment of all NMR signals.

Topics: Acetates; Antifungal Agents; Benzofurans; Magnetic Resonance Spectroscopy; Molecular Structure; Oxepins; Stereoisomerism