Hybrid Diterpenic Meroterpenoids from an Endophytic Penicillium sp. Induced by Chemical Epigenetic Manipulation.

Cultivation of an endophytic fungus Penicillium sp. KMU18029 with suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, led to the isolation of two pairs of diterpenic meroterpenoids with a unique natural product framework combining features of pyripyropenes and decaturins/oxalicines, pyrandecarurins A ( 1 ) and B ( 2 ), pileotin A ( 3 ) and B ( 4 ), along with their potential precursor decaturenoid ( 5 ). Compounds 1 , 2 , 4 , and 5 were new. The structures of 1 - 5 were elucidated by extensive spectroscopic analyses. The absolute configurations of 1 - 4 were determined by single-crystal X-ray diffraction, NOESY spectra, ECD calculations, and biogenetic considerations. The absolute configuration of compound 3 was confirmed for the first time. Compound 5 showed moderate activity against AChE with an IC 50 value of 13.9 ± 1.1 μM.