In our study on lipoxygenase inhibitors, we succeeded in designing a new assay system. Furthermore, we found four novel lipoxygenase inhibitors, tetrapetalone A (1), B (2), C (3) and D (4) by using this system. Tetrapetalone A (1), B (2), C (3) and D (4) were isolated from a culture filtrate of Streptomyces sp. USF-4727 strain. The planar structure of 1 was determined by its spectroscopic evidence and methylation with diazomethane to show the presence of a novel tetracyclic skeleton, including a nitrogen atom, and a β-rhodinosyl moiety in 1. The stereochemistry of 1 was investigated by the coupling constant in the ^1H NMR spectrum, NOE correlations and modified Mosher's method. Then, the absolute stereochemistry of all the asymmetric carbons was determined. In the similar way, we estimated the chemical structure of 2, 3 and 4. Tetrapetalone B (2) also had a tetracyclic skeleton and a β-rhodinosyl moiety as well as 1. Tetrapetalone B (2), however, had an additional acetoxy moiety at a side chain of the tetracyclic skeleton. Tetrapetalone C (3) and D (4) were revealed to be derivatives of 1 and 2, respectively, with an additional hydroxy group in their tetracyclic skeleton. Tetrapetalone A (1), B (2), C (3) and D (4) indicated the inhibitory activity against soybean lipoxygenase as well as two well-known lipoxygenase inhibitors, kojic acid and NDGA.
