Structure, Synthesis, and Biological Properties of Kalkitoxin, a Novel Neurotoxin from the Marine Cyanobacterium Lyngbya majuscula

Cyanobacteria from a diversity of marine and freshwater habitats are known to produce neurotoxic secondary metabolites. Herein, we describe the complete stereostructure, synthesis, and biological properties of kalkitoxin (1), a novel neurotoxic lipopeptide from a Caribbean collection of Lyngbya majuscula. The organic extract of this L. majuscula exhibited potent brine shrimp and fish toxicity. Using these assays, the toxic metabolite kalkitoxin (1), was isolated by sequential silica gel VLC, CC, and normal-phase HPLC (12.8 mg, 0.3% of extract). Subsequently, bioassay-guided fractionation using a primary cell culture of rat neurons in a microphysiometer or inhibition of IL-1 beta stimulation of sPLA sub(2) in hepatocarcinoma cells led to re-isolation of 1 in small yield from various Caribbean collections of L. majuscula.