Nebulosins: Trisubstituted Thiolane Natural Products from the Northeastern Atlantic Annelid Eupolymnia nebulosa

Using both multi-informative molecular network and score-based approaches as prioritization strategies, the Northeastern Atlantic marine terebellid Eupolymnia nebulosa was selected for in-depth chemical investigation. A family of 16 new metabolites named nebulosins was isolated and structurally characterized from extensive analyses of HRMS/MS and NMR spectroscopic data. Nebulosins feature an unprecedented highly substituted thiolane ring leading to up to four contiguous chiral centers. The relative configurations were assigned through a combination of NOESY analysis, spin-spin coupling constant analysis, and NMR chemical shifts measurements, while the absolute configurations were determined by comparison between experimental and theoretical ECD spectra. This family of natural product exhibits promising antioxidant activities in both ORAC and ROS assays.