Polyketides with Anti-Inflammatory Activity from Trichoderma koningiopsis, a Rhizosphere Fungus from the Medicinal Plant Polygonum paleaceum

Abstract

Twelve new fungal polyketides, koningiopisins I–P (1–8) and trichoketides C–F (9–12), together with six known congeners (13–18), were isolated from Trichoderma koningiopsis, a rhizosphere fungus obtained from the medicinal plant Polygonum paleaceum. Their structures and absolute configurations were established by spectroscopic analysis, single-crystal X-ray diffraction, the modified Mosher’s method, chemical derivatization, the octant rule, and 13C NMR and ECD calculations. Compounds 1–5 are tricyclic polyketides possessing an octahydrochromene framework with a 6,8-dioxabicyclo[3.2.1]­octane core. Compounds 7 and 8 contain a unique ketone carbonyl group at C-7 and differ from other members of this group of compounds with the ketone carbonyl group at C-1. Compounds 1, 2, and 13 showed inhibitory activity on LPS-induced BV-2 cells on NO production with IC50 values of 14 ± 1, 3.0 ± 0.5, and 8.9 ± 2.7 μM, respectively.

Cooperative Rh/Achiral Phosphoric Acid-Enabled [3+3] Cycloannulation of Carbonyl Ylides with Quinone Monoimines: Synthesis of Benzofused Dioxabicyclo[3.2.1]octane Scaffolds

“…2 Koningiopisins I−K, bearing a dioxabicyclo [3.2.1]octane core, isolated from a rhizosphere fungus of medicinal plant Polygonum paleaceum, showed antiinflammatory activity on LPS-induced BV-2 cells with regard to NO production. 3 Koninginin A exhibits substantial antibiotic activity toward the take-all fungus. 4 Therefore, the development of new, efficient, and straightforward synthetic methods for the rapid construction of structurally complex polycyclic oxa-bridged scaffolds is highly desirable.…”

“…Werz and co-workers reported the [3+3] cycloaddition of carbonyl ylides with donor−acceptor cyclopropanes under cooperative Rh/Lewis acid catalysis giving access to 9-oxabicyclo[3.3.1]nonan-2-one and 10oxabicyclo[4. 3.1]decen-2-ol cores. 9 Schneider and co-workers described the cooperative Rh/chiral phosphoric acid-catalyzed [3+3] cycloannulation of carbonyl ylides and indolyl-2methides, furnishing oxa-bridged azepino[1,2-a]indoles.…”

“…The product was obtained by column chromatography on silica gel (eluent, 5:1 petroleum ether/ethyl acetate) as a white solid (78.0 mg, 70% yield): mp 150−151 °C; 1 H NMR (600 MHz, DMSO-d 6 ) δ 10.01 (s, 1H), 7.64−7.61 (m, 2H), 7.57−7.54 (m, 3H), 7.42 (td, J = 7.6, 0.9 Hz, 1H), 7.36 (td, J = 7.5, 0.9 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 2.6 Hz, 1H), 7.10−7.08 (m, 3H), 6.94 (dd, J = 8.8, 2.6 Hz, 1H), 6.79 (d, J = 8.7 Hz, 1H), 4.49−4.44 (m, 1H), 4.44−4.39 (m, 1H), 3.82 (s, 3H), 2.34 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H); 13 C{ 1 H} NMR (150 MHz, DMSO-d 6 ) δ 165. 9, 160.7, 147.2, 143.9, 143.7, 138.3, 136.6, 131.1, 130.2, 130.0 (2C), 129.8, 129.8, 128.2 (2C), 127.9, 127.2 (2C), 126.1, 124.9, 123.9, 122.7, 119.9, 118.4, 115.2, 114.3 (2C), 107.5, 84.8, 62.8, 55.7, 21.4, 14.4 Ethyl 6- (3,sulfonamido]-6,11-epoxydibenzo [b,e]oxepine-11(6H)-carboxylate (3fa). The product was obtained by column chromatography on silica gel (eluent, 5:1 petroleum ether/ethyl acetate) as a white solid (76.3 mg, 65% yield): mp 171−172 °C; 1 H NMR (600 MHz, CDCl 3 ) δ 7.59 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 8.2 Hz, 2H), 7.38 (dd, J = 8.4, 1.9 Hz, 1H), 7.33−7.27 (m, 3H), 7.18 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 2.5 Hz, 1H), 7.09 (d, J = 7.3 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.90 (dd, J = 8.7, 2.5 Hz, 1H), 6.74 (d, J = 8.7 Hz, 1H), 6.56 (s, 1H), 4.52−4.47 (m, 1H), 4.46−4.41 (m, 1H), 3.93 (s, 2H), 3.90 (s, 3H), 2.38 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H); 13 C{ 1 H} NMR (150 MHz, CDCl 3 ) δ 166.…”

“… Claulansine A showed selective neuroprotective effects . Koningiopisins I–K, bearing a dioxabicyclo[3.2.1]­octane core, isolated from a rhizosphere fungus of medicinal plant Polygonum paleaceum , showed anti-inflammatory activity on LPS-induced BV-2 cells with regard to NO production . Koninginin A exhibits substantial antibiotic activity toward the take-all fungus .…”

Maydistacins A–G, Terpestacin-type Sesterterpenoids with Anti-inflammatory Activity from the Phytopathogenic Fungus Bipolaris maydis

“…Inflammation is a protective reaction of a host to infection or injury. − In this complex process, nitric oxide (NO) is recognized as a crucial regulator, and the overproduction of NO is implicated in various inflammatory disorders, such as arthritis, asthma, and cardiovascular disease . The use of pharmaceuticals to inhibit the production of NO is a significant therapeutic method to slow or reverse the pathogenesis of those inflammatory disorders, − and there is still an urgent need for the development of novel anti-inflammatory drugs with NO production inhibitory activity. , …”