lyngbyastatin-1 and lyngbyastatin-3

A Papua New Guinea field collection of the marine cyanobacterium Blennothrix cantharidosmum was investigated for its cytotoxic constituents. Bioassay-guided isolation defined the cytotoxic components as the known compounds lyngbyastatins 1 and 3. However, six new acyl proline derivatives, tumonoic acids D-I, plus the known tumonoic acid A were also isolated. Their planar structures were defined from NMR and MS data, while their stereostructures followed from a series of chiral chromatographies, degradation sequences, and synthetic approaches. The new compounds were tested in an array of assays, but showed only modest antimalarial and inhibition of quorum sensing activities. Nevertheless, these are the first natural products to be reported from this genus, and this inspired a detailed morphologic and 16S rDNA-based phylogenetic analysis of the producing organism.

Topics: Animals; Antimalarials; Cyanobacteria; DNA, Bacterial; Drug Screening Assays, Antitumor; Lyngbya Toxins; Microbial Sensitivity Tests; Molecular Structure; Oligopeptides; Papua New Guinea; Peptides, Cyclic; Proline; Quorum Sensing; RNA, Ribosomal, 16S

The structure of lyngbyastatin 3 (1), including the configurations of the two unusual amino acid residues, viz., the 3-amino-2-methylhexanoic acid (Amha) and 4-amino-2,2-dimethyl-3-oxopentanoic acid units (Ibu), has been established by chemical degradation. Analysis of the cyanobacterial samples of lyngbyastatin 3 (1), lyngbyastatin 1 (2), and dolastatin 12 (3) demonstrated that they are mixtures of Ibu epimers [R (major) and S (minor)], whereas the structurally related majusculamide C (4) is a single diastereomer having an S-Ibu unit.

Topics: Amino Acids; Chromatography, High Pressure Liquid; Cyanobacteria; Depsipeptides; Gas Chromatography-Mass Spectrometry; Guam; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides; Peptides, Cyclic; Stereoisomerism