Pochobulbins A-F, Immunosuppressive Secopenitrem-Type Indole Diterpenoids from an Endophytic Pochonia bulbillosa.

Three monoclavatol-secopenitrems (1-3), one bis-clavatol-secopenitrem (4), and two bis-5-methylpyrogallol-secopenitrems (5 and 6) were obtained from the endophytic fungus Pochonia bulbillosa KNI755. Pochobulbins A-F (1-6) are the initial instances of secopenitrem-type indole diterpenoids with a 4/6/6/5/5/6/6/6/6/6 fused decacyclic ring system. Compounds 1-4 feature a secopenitrem skeleton fused to a clavatol unit via a tetrahydro-2H-pyran bridge. Compounds 5 and 6 are the first secopenitrem-type indole diterpenoids that connect a 5-methylpyrogallol unit to a secopenitrem unit via a 1,4-dioxane bridge. The complete structures, including their absolute stereochemical assignments, were determined through comprehensive spectroscopic analyses and ECD simulations. Compounds 1, 3, and 5 inhibited T cell proliferation, and compounds 1 and 3 also inhibited B cell proliferation, exhibiting EC50 values between 4.6 and 13 μM.