In our search for bioactive compounds from marine microorganisms, we have examined extracts of symbiotic bacteria associated with various marine invertebrates and isolated a new cytotoxic alkaloid, alteramide A (1), from the cultured mycelium of a bacterium Alteromonas sp. separated from the marine sponge Halichondria okadai. The molecular formula of 1 was determined to be C_<29>H_<38>N_2O_6 on the basis of HRFABMS. The ^1H and ^<13>C NMR spectra of 1 indicated the presence of a dienone and a dienoyltetramic acid. The whole structure of 1 was elucidated by extensive analyses of ^1H-^1H COSY, HMQC, and HMBC spectra and the relative stereochemistry of 1 was established by the NOESY spectrum of compound 2 derived from 1. The hexacyclic derivative 3 was generated photochemically from 1 through a unique intramolecular [4+4] cycloaddition. Alteramide A (1) exhibited cytotoxicities against murine leukemia P388 cells, murine lymphoma L1210 cells, and human epidermoid KB cells in vitro with the IC_<50> values of 0.1, 1.7, and 5.0μg/mL, respectively, while compound 3 showed no cytotoxicity.
