Brominated bitter compounds from the skin tubercle gland of the stonefish <i>Synanceia verrucosa</i>

The skin tubercle gland of the stonefish Synanceia verrucosa secretes "ichthyocrinotoxin." Ichthyocrinotoxins have been suggested to act as antifeedants against predators and as anthelmintics against parasites. Three novel compounds, synanceins A (1), B (2), and C (3), were isolated from S. verrucosa skin tubercle gland secretions as the major compounds. Their absolute structures were determined unambiguously by synthesizing molecular fragments and applying a modified Mosher's method. Compounds 1-3 are the first examples of brominated natural products from vertebrates. These compounds did not show any toxic activity against the L1210 cell lines and a marine diatom at a concentration of 100 μm. However, three researchers, who were the subjects, perceived a strong bitter taste at 10 μg of compounds 1-3. Synanceins A (1), B (2), and C (3), the major compounds in the ichthyocrinotoxin fraction of S. verrucosa, may play important roles as anthelmintics and antifeedants.