Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821

Eight new decahydrofluorene-class alkaloids, microascones A and B ( 1 and 2 ), 2,3-epoxyphomapyrrolidone C ( 3 ), 14,16-epiascomylactam B ( 4 ), 24-hydroxyphomapyrrolidone A ( 5 ), and microascones C–E ( 6 – 8 ), along with five known analogs ( 9 – 13 ) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13 C NMR chemical shifts. Compounds 10 – 13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure–bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1 – 8 was also proposed.