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

Abstract 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, 13 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 50 values ranging from 0.01 to 4.45 μM.