Abstract
A number of previously undescribed (1-7) and structurally related known (8-17) isobenzofuran-type polyketides were obtained from the fermentation of Penicillium commune P-4-1, an endophytic fungus isolated from the fresh trunk bark of the critically endangered conifer Abies beshanzuensis. Beshanzoides A-D (1-4, resp.) feature a cycloheptanone-containing isobenzofuran ring system hitherto unknown, which might be biosynthesized via two steps of aldol reactions starting from a common co-occurring isobenzofuran-type polyketide as the precursor. The new structures were elucidated by spectroscopic methods, electronic circular dichroism data, and single crystal X-ray diffraction analyses. Beshanzoide E (5) showed antimicrobial activity (MIC: 16 μg mL(-1)) against Staphylococcus aureus, whereas (±)-strobide A (10) inhibited (MIC: 16 μg mL(-1)) Candida albicans. Cyclopaldic acid (12) and 3-O-methyl-cyclopaldic acid (13) exhibited inhibitory effects against acetyl-CoA carboxylase 1 (ACC1) with IC(50) values of 0.96 and 11.77 μM, respectively. Compound 12 also inhibited (IC(50): 7.56 μM) ATP-citrate lyase (ACL).