Pochobulbins A–F, Immunosuppressive Secopenitrem-Type Indole Diterpenoids from an Endophytic <i>Pochonia bulbillosa</i>

Three monoclavatol-secopenitrems (<b>1</b>-<b>3</b>), one bis-clavatol-secopenitrem (<b>4</b>), and two bis<b>-</b>5-methylpyrogallol-secopenitrems (<b>5</b> and <b>6</b>) were obtained from the endophytic fungus <i>Pochonia bulbillosa</i> KNI755. Pochobulbins A-F (<b>1</b>-<b>6</b>) 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 <b>1</b>-<b>4</b> feature a secopenitrem skeleton fused to a clavatol unit via a tetrahydro-2<i>H</i>-pyran bridge. Compounds <b>5</b> and <b>6</b> 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 <b>1</b>, <b>3</b>, and <b>5</b> inhibited T cell proliferation, and compounds <b>1</b> and <b>3</b> also inhibited B cell proliferation, exhibiting EC₅₀ values between 4.6 and 13 μM.