JBIR-15

Eleven new aspochracin-type cyclic tripeptides, sclerotiotides A-K (1-11), together with three known compounds, JBIR-15 (12), aspochracin (13), and penicillic acid, were isolated from the ethyl acetate extract of the fermentation broth of the halotolerant Aspergillus sclerotiorum PT06-1 in a hypersaline nutrient-rich medium. Their structures were elucidated by spectroscopic analysis and chemical methods. Chemical transformations of 12 and 13 proved that sclerotiotides D-K (4-11) were artifacts probably formed during the fermentation or subsequent isolation steps. All 13 cyclic tripeptides have been evaluated for their antimicrobial and cytotoxic effects. Only sclerotiotides A (1), B (2), F (6), and I (9) and JBIR-15 (12) showed selective antifungal activity against Candida albicans with MIC values of 7.5, 3.8, 30, 6.7, and 30 microM, respectively.

In the course of our chemical screening program for novel metabolites by LC-MS monitoring, we isolated a new aspochracin derivative, JBIR-15 (1), together with aspochracin, from the culture broth of a sponge-derived fungus, Aspergillus sclerotiorum Huber Sp080903f04. The structure of 1 was determined to be N-demethyl aspochracin at the alanyl residue on the basis of extensive NMR and MS analyses.