Ascomycotols A–C: Rare Sulfur/Sulfone-Containing Scaffolds from Mushroom Endophytes with Dual Anti-inflammatory and Antirenal Fibrosis Effects

Endophytic fungal natural products, especially sulfur- or sulfone-containing scaffolds, have attracted increasing attention as a valuable resource for drug development. Ascomycotol A ( 1 ), a polyketide with an unprecedented 4-oxa-12-thiabicyclo[7.3.1]tridecane sulfur-containing scaffold, and ascomycotols B ( 2 ) and C ( 3 ) featuring rare sulfone functional moieties, were purified from the mushroom ( Ganoderma species)-associated endophytic Ascomycota sp. GLQ01 and Trichoderma harzianum GLQ03. Their chemical structures were assigned using nuclear magnetic resonance data, electronic circular dichroism calculations, and X-ray diffraction methods. A possible biosynthetic pathway of compounds 1 – 3 was speculated, involving two consecutive S-nucleophilic addition reactions and atypical incorporation of both l -Phe and d -Phe residues. Finally, biological activity studies revealed that compounds 1 and (+)- 2 exhibit the potential of anti-inflammatory activity, and compound 1 has a dose-dependent protective effect on age-related renal fibrosis in vitro .