Citrinin Monomer, Trimer, and Tetracyclic Alkaloid Derivatives from the Hydrothermal Vent-Associated Fungus Penicillium citrinum TW132-59.

Five new unusual citrinin-derived alkaloids with a tetracyclic core, citrinidines A-E ( 1 - 5 ), two new amide alkaloids, methyl (2 S ,8 E )-1'-(2-methyl-3-oxodec-8-enamido) butanoate ( 6 ) and (2 S ,8 E )-2-methyl-3-oxodec-8-enamide ( 7 ), a new unusual citrinin trimer, tricitrinol C ( 8 ), a new citrinin acetal-ketal derivative, citrininol ( 9 ), together with four known citrinin monomers ( 10 - 13 ), and three known citrinin dimers ( 14-16 ), were isolated from the fermentation of hydrothermal vent-associated fungus Penicillium citrinum TW132-59. Their structures were unambiguously determined by nuclear magnetic resonance (NMR), mass spectrometry, Mosher's method, 13 C NMR calculation in combination with DP4+, and ECD calculations. A plausible biosynthetic pathway of all new compounds ( 1 - 9 ) was proposed. Citrinin trimer ( 8 ) exhibited potent cytotoxicity activity with an IC 50 value of 1.34 ± 0.11 μM, and compounds 1 and 15 showed moderate cytotoxicity with IC 50 values of 17.50 ± 1.43 and 9.45 ± 0.55 μM, respectively, against A549 cell line.