Nitropyrrolins A-E, Cytotoxic Farnesyl-alpha-nitropyrroles from a Marine-Derived Bacterium within the Actinomycete Family Streptomycetaceae

Abstract

Five new farnesyl-alpha-nitropyrroles, nitropyrrolins A-E (1-5), were isolated from the saline culture of the marine actinomycete strain CNQ-509. This strain belongs to the "MAR4" group of marine actinomycetes, which have been demonstrated to be a rich source of hybrid isoprenoid secondary metabolites. The structures of the nitropyrrolins are composed of alpha-nitropyrroles with functionalized farnesyl groups at the C-4 position. These compounds are the first examples of naturally occurring terpenyl-alpha-nitropyrroles. Chemical modifications, including one-step acetonide formation from an epoxide, and application of the modified Mosher method provided the full stereostructures and absolute configurations of these compounds. Several of the nitropyrrolins, nitropyrrolin D in particular, are cytotoxic toward HCT-116 human colon carcinoma cells, but show weak to little antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).