Identification of Boletopsin 11 and 12, Antibiotics from the Traditionally Used Fungus Boletopsis sp.

Abstract

Magic mushrooms: The investigation of an edible Boletopsis mushroom that is used traditionally in Papua New Guinea as treatment for gastrointestinal complaints led to the discovery of two new heterocyclic p‐terphenyl ethers, boletopsin (1) and 12 (2), along with the known metabolites boletopsin 4 and 7 and cycloleucomelone. Evaluation of the antibiotic activity of the compounds isolated from this Boletopsis sp. supported the traditional medicinal use of the mushroom.

Syntheses of the Fungal Metabolites Boletopsins 7, 11, and 12 from the Papua New Guinea Medicinal Mushroom Boletopsis sp.

“…The purified synthetic compounds 1− 3 showed activity comparable to that of the natural isolates, 6 while the activity of 16 and 20 suggested that the 4′-OMe group is not crucial in the activity of the boletopsins.…”

“…The characteristic data for synthetic boletopsin 11 were identical with those of natural boletopsin 11. 6 The formation of boletopsin 7 (1) was achieved by the treatment of 20 with boron tribromide at −78°C, giving the tetrahydroxy pterphenyl in 68% yield (Scheme 6). The data for synthetic boletopsin 7 were identical with those of the natural boletopsin 7.…”

“…Purification was achieved via flash column chromatography on silica using 25% EtOAc in petroleum ether as eluent (R f = 0.2), yielding a white amorphous solid (48%, 190 mg, 0.413 mmol). 1 [1,3]dioxole-5-carbaldehyde (6). A solution of 15 (190 mg, 0.413 mmol), 9 (69 mg, 0.454 mmol), cesium carbonate (269 mg, 826 mmol), water (0.20 mL), and toluene (10 mL) was degassed by a freeze/thaw process three times and placed under an atmosphere of argon.…”

Discovery and Synthesis of Boletopsins 13 and 14, Brominated Fungal Metabolites of Terrestrial Origin

“…used traditionally by the Kiovi Tribe of the Lufa District in the Eastern Highlands as a food source and as a treatment for gastrointestinal complaints. 1 It is widely accepted among natural product chemists that terrestrial fungi do not produce brominated metabolites, 2 but during our investigation of the chemistry of this fungus we discovered two polybrominated compounds, reported here as boletopsins 13 (1) and 14 (2) (Figure 1). We report here the isolation and definitive structural elucidation, through synthesis, of the first polybrominated metabolites, boletopsin 13 and boletopsin 14, to be isolated from a terrestrial fungus.…”

Total Synthesis of Suillusin

“… Structural elucidation of the natural product was achieved using NMR and mass spectrometry, suggesting the connectivity and the relative stereochemistry of the densely substituted 1 H -cyclopenta­[ b ]­benzofuran. In the isolation report, it was hypothesized that suillusin ( 1 ) biosynthetically originates from polyporic acid, thus sharing a common metabolic precursor with the p -terphenyl natural product family (e.g., ganbajunin 8 ( 2 ) and boletopsin 11 ( 3 )). Notably, fungal metabolites that feature the densely functionalized 1 H -cyclo­penta­[ b ]­benzo­furan core are relatively atypical among other members of the arylpyruvic acid p -terphenyl family, raising questions surrounding suillusin’s biosynthetic origin.…”