Dibrefeldins A and B, A pair of epimers representing the first brefeldin A dimers with cytotoxic activities from Penicillium janthinellum.

Dibrefeldins A and B (1 and 2), two unexpected brefeldin A (BFA) dimers, as well as brefeldin F (3), brefeldin G (4), and 14-hydroxy-BFA (5), three new BFA derivatives, together with three new naturally occurring BFA derivatives (6-8) and four known analogues (9-12), were isolated from the fungus Penicillium janthinellum. Dibrefeldins A and B (1 and 2) represent the first examples of BFA dimers formed by an esterification between two BFA monomer units. Brefeldin F (3) has an α,β-unsaturated γ-lactone ring, and this moiety was first discovered in naturally occurring BFA derivatives. The structures and relative/absolute configurations of these derivatives were elucidated by extensive spectroscopic methods, C NMR calculations, and single-crystal X-ray diffraction. Compounds 1, 2, 8, and 9 showed excellent cytotoxic activities against six cancer cell lines with IC values ranging from 0.01 to 4.45 μM.