Asperosin A, a [4 + 2] Diels–Alder cycloaddition polyketide dimer from Aspergillus rugulosa with immunosuppressive activity

A novel homologous polyketide dimer, asperosin A (1), constructed with a unique hetero-bicycle 6/5 ring system featuring four continuous quaternary carbons, was isolated from a solid culture of the fungus Aspergillus rugulosa. The structure of 1 was elucidated by extensive 400 MHz and 600 MHz nuclear magnetic resonance (NMR) spectroscopy analysis, electronic circular dichroism (ECD) calculations, DP4+ probability analysis, and a detailed discussion of its biosynthetic origin. Biogenetically, compound 1 was constructed from two identical original polyketides via the intermolecular [4 + 2] Diels–Alder cycloaddition reaction. It is notable that compound 1 displayed remarkable immunosuppressive activity in murine splenocytes and human T cells stimulated by anti-CD3/anti-CD28 monoclonal antibodies.