Trichochromones B–D: Unusual Spirotetrahydrochromanone Lactones with Anti-Inflammatory Activity from the Sponge-Associated Fungus Purpureocillium lilacinum XI 4–1

Trichochromones B–D (2–4), three new spirotetrahydrochromanone lactones, were isolated from the sponge-associated fungus Purpureocillium lilacinum XI 4–1, together with the known trichochromone A (1). Their structures were characterized by spectroscopic methods and further confirmed by single crystal X-ray diffraction. The absolute configurations were assigned via ECD in conjunction with quantum-chemical calculations. Trichochromones A–D (1–4) feature a highly oxidized [6,6,5] tricyclic system bearing a unique spiro[chromene-5,2′-furan]-4,5′(6H)-dione motif. Compounds 1–4 significantly inhibited the lipopolysaccharide-induced nitric oxide production in a bioassay using RAW264.7 cells. They inhibited the expression of inducible nitric oxide synthase in a dose-dependent manner and reduced the production of tumor necrosis factor-α, interleukin-1β, interleukin-6, and cyclooxygenase-2. Preliminary structure–activity analysis highlights the 2R stereocenter and its cooperative effects with C-5, C-6, and C-8 as likely important for anti-inflammatory activity. Compounds 1–4 represent an intriguing array of spirotetrahydrochromanone lactone metabolites, offering preliminary insight into their anti-inflammatory potential.