Hemivannusal and Prevannusadials – New Sesquiterpenoids from the Marine Ciliate Protist Euplotes vannus: The Putative Biogenetic Precursors of Dimeric Terpenoid Vannusals

Hemivannusal (6), a bicyclic sesquiterpenoid with an unprecedented skeleton, has been isolated from the marine ciliate Euplotes vannus (strain TB6). The relative configuration of 6 has been established through an extended conformational search performed by molecular mechanics and refined through ab initio quantum chemical calculations. Another strain (CM1) of the same morphospecies has been found to produce the linear prevannusadial A (7) and the monocyclic prevannusadial B (8), which could represent key intermediates for the biosynthesis both of hemivannusal (6) and of the C30 terpenoids vannusals A and B (5a and 5b), the latter pair being metabolites isolated from conspecific strains (Sil21 andBUN3) of the same E. vannus morphospecies. The occurrence of hemivannusal (6) in mass cell cultures both of an E. vannus endosymbiont-free strain and of a penicillin-treated E. vannus bacteria-infected strain strongly suggests that its biosynthesis is coded by the ciliates and not by prokaryotic endosymbiont genes. The pattern of the secondary metabolites isolated so far from different strains of E. vannus allows us not only to assign them a chemotaxonomic significance, but also to propose a unifying picture of their biogenesis.