A Novel Lactam and Two Rare Mycophenolic Acid Derivatives from the Fungus Penicillium sclerotiorum JBHL321

A novel lactam penicillactam (1), two rare mycophenolic acid (MPA) derivatives penimycophens A and B (2 and 3), together with two known biogenetically related MPA derivatives (4 and 5) and a known alkaloid (6) were isolated from the Penicillium sclerotiorum JBHL321. The structures of these compounds were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD) calculations. Compound 1 represent the rare example of a oxygen bridge‐linked lactam from natural products. Structurally, compounds 2 and 3 were rare MPA derivatives featuring a methoxy group at C‐3. The inhibitory activity of compounds 1‐6 against two phytopathogenic fungi, three phytopathogenic bacteria and four cancer cell lines were evaluated. Compounds 2‐5 exhibited significant cytotoxic activity against HeLa, MCF‐7, A549 and MGC‐803 cells with IC50 values in the low micromolar to nanomolar. Compound 3 exhibited especially cytotoxic activity against four different cell lines with IC50 values ranging from 0.06 to 0.14 μM, compared to IC50 values ranging from 0.62 to 2.51 μM for epirubicin.