Ergochaeglobosins A—E, Unprecedented Heterodimers of Cytochalasan and Ergosterol from Chaeglobosin globosum P2-2-2

Five novel heterodimers of cytochalasan and ergosterol,ergochaeglobosins A—E,were isolated from an endophytic fungus Chaetomium globosum P2-2-2.Ergochaeglobosin A(1) possesses an unprecedented 5/6/13/6/5/6/6/6 fused octacyclic ring system,and ergochaeglobosins B(2) and C(3) form a unique 5/6/13/6/6/6/6/5 fused octacyclic ring system,whereas ergochaeglobosins D(4) and F(5) are the first cytochalasan heterodimers formed via a N-1′/C-3′′single bond.Their structures with absolute configurations were established by extensive spectroscopic analyses,single-crystal X-ray diffraction,and ECD calculations.The plausible biogenetic pathway of 1—5 was postulated.Compound 1 exhibited inhibitory effects against ConA-induced T cells and LPS-induced B cells proliferation with IC50 values of 19.2 and 14.1μmol/L,respectively.Co-treatment of 3(20μmol/L)with TRAIL(150 ng/mL)could significantly decrease the cell viability of A549 by 24.9%comparing with monotherapy of 3(20μmol/L).