Phaeosphaones: Tyrosinase Inhibitory Thiodiketopiperazines from an Endophytic .

, an endophytic fungus associated with the herbal medicine , produced four new thiodiketopiperazine alkaloids, phaeosphaones A-D (-), featuring an unusual β-(oxy)thiotryptophan motif, along with four known analogues, phaeosphaone E (), chetoseminudin B (), polanrazine B (), and leptosin D (). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. Compounds , , and were found to display mushroom tyrosinase inhibitory activity with IC values of 33.2 ± 0.2, 31.7 ± 0.2, and 28.4 ± 0.2 μM, respectively, more potent than that of the positive control, kojic acid (IC = 40.4 ± 0.1 μM). A molecular-docking study disclosed the π-π stacking interaction between the indole moiety of and the His243 residue of tyrosinase.