Parazoanthines A-E: Hydantoin Alkaloids from the Mediterranean Sea Anemone Parazoanthus axinellae

Abstract

Five new hydantoin alkaloids, named parazoanthines A-E (1-5), were isolated as the major constituents of the Mediterranean sea anemone Parazoanthus axinellae. Their structural elucidation was achieved through NMR spectroscopic and mass spectrometric analyses. The absolute configuration of the chiral compounds 1 and 4 was determined by comparison between experimental and TDDFT calculated CD spectra. The configuration of the trisubstituted double bond of 2, 3, and 5 was deduced from the 3JH6-C4 coupling constant value. This family of alkaloids represents the first example of natural 3,5- disubstituted hydantoins which do not exhibit a methyl at N-3. All compounds were tested for their natural toxicity (Microtox® assay) and parazoanthine C (3) exhibited the highest natural toxicity. 3 Relatively few chemical studies of zoanthids have been reported so far, despite evidence of their rich natural products chemistry.1 Colonial sea anemones of the genus Parazoanthus have been identified in almost all the oceans and they often have been described as epibionts of marine sponges belonging to the Agelas or Axinella genera. As sponges are known to exude toxic compounds, these zoanthids must have developed adaptative tools to minimize effects of such toxins. Two groups of compounds have been described from Parazoanthus species: fluorescent guanidine alkaloids of the zoanthoxanthin families,2-7 and ecdysteroids.8 As part of an ongoing research program to investigate the chemodiversity of Mediterranean invertebrates,9 specimens of Parazoanthus axinellae were collected near Marseilles (Plane island) as epibionts of the sponge Axinella damicornis. Because the LC–MS analyses of their crude extracts evidenced brominated compounds as major constituents, we decided to undertake the full chemical study of this species from which only zoanthoxanthins have been previously described.2,3 We report herein the isolation and structural characterization of a new class of alkaloids named parazoanthines A-E (1-5) with a rare 3,5-disubstituted hydantoin core.