Cratenin, a Rare Oxylipin Marking Kleptopredation in Aeolid Nudibranchs

Marine mollusks of the order Nudibranchia produce a wide array of secondary metabolites that play key roles in predator-prey interactions and often exhibit remarkable bioactivity. In this study, a chemical investigation of the Mediterranean aeolid nudibranchs <i>Cratena peregrina</i> and <i>Paraflabellina ischitana</i> led to the isolation and characterization of a novel oxylipin, designated cratenin (<b>1</b>). This unique metabolite shows an unusual alkylated monosubstituted tetrahydrofuran (THF) moiety, a structural feature rarely encountered among marine natural products. The planar structure of <b>1</b> was fully elucidated by high-resolution mass spectrometry (HRMS) and comprehensive 1D and 2D NMR spectroscopy, while the absolute configuration of the substituted THF ring was rigorously established by chemical degradation, derivatization, and NMR-based stereochemical comparison with known diasteromeric derivatives of (tetrahydrofuran-2-yl)methanol. The co-occurrence of cratenin (<b>1</b>) in the hydrozoan <i>Eudendrium racemosum</i>, a known prey of <i>C. peregrina</i> and other aeolid nudibranchs, strongly suggests its role as a semiochemical which mediates predator-prey interactions. The proposed biosynthetic origin of cratenin (<b>1</b>) from algal docosahexaenoic acid (DHA) further corroborates the hypothesis of dietary acquisition and provides compelling molecular evidence for kleptopredation, a sophisticated foraging behavior where nudibranchs consume prey that has recently ingested phytoplankton. In this view, this study reveals a clear metabolic and ecological link connecting phytoplankton, hydrozoans, and nudibranchs, underscoring the pivotal role of lipid-derived natural products in shaping chemical communication and interphyletic trophic interactions involving opisthobranchs.