Sorbicillinoids with anti-inflammatory activity from the mangrove sediment-derived fungus Trichoderma reesei SCSIO...

Thirteen new sorbicillinoids including trichosorbicilloid A (1), 12-epi- trichosorbicilloid A (2), trichosorbicilloids B - C (3-4), 24-hydroxy-12-epi-trichobisvertinol D (5), 15,24-dihydroxy-12-epi-trichobisvertinol D (6), 15,24-dihydroxy-13,14-tetrahydro-12-epi-trichobisvertinol D (7), 15-hydroxy-13,14-tetrahydro-12-epi-trichobisvertinol D (8), 24-hydroxy-trichobisvertinol D (9), 15,24-hydroxy-trichobisvertinol D (10), 13,20-dihydroxy-trichodermolide (11), 20-hydroxy-13-trichodermolide acid (12), and trichosorbicilloid D (13) were isolated from the mangrove sediment-derived fungus Trichoderma reesei SCSIO 41705. Their structures were determined by extensive spectroscopic analysis, and their absolute configurations were established by quantum chemical calculations of electronic circular dichroism (ECD) spectra or comparison of experimental ECD spectra. Compounds 1 and 2 possess a novel cagelike polycyclic skeleton with a unique 5/5/5/5/6 ring system. Compound 3 was the first example of hybrid sorbicillinoid fused vertinolide with a 3-propyl-1H-indole unit by Michael-addition. Compounds 5-13 as dimeric sorbicillinoids have different sorbyl side chains. Biologically, compounds 3, 11 and 13 showed potent anti-inflammatory activity by inhibiting the LPS-induced NO production in RAW 264.7 cells. A preliminary structure-anti-inflammatory activity relationship of sorbicillinoids was also discussed.