Bisaspochalasins A-C: Three Cytochalasan Homodimers with Highly Fused Ring System from an Endophytic Aspergillus flavipes.

ABSTRACT

Three unprecedented cytochalasan homodimers, bisaspochalasins A-C (1-3), and two known monomers, aspochalasins B and D (4 and 5), were isolated from an endophytic Aspergillus flavipes. Bisaspochalasin A (1) contains a 13-hydroxy-3,24-dioxatricyclo[11.10.11,13.02,15]tetracos-4-one cross-linkage, representing an unprecedented carbon skeleton. Bisaspochalasins B (2) and C (3) share a thioether bridge, while 3 has a peroxy modification at C-7, which may be generated by Schenck-ene photooxygenation. Their structures, including their absolute configurations, were elucidated by HRESIMS, NMR, chemical transformation, and X-ray crystallography. Bisaspochalasin A showed inhibitory activity against human T cell proliferation with an IC50 value of 15.8 µM while maintaining low cytotoxicity to T cells.