Norterpene Cyclic Peroxides from the Marine Sponge , Inhibitors of Transient Receptor Potential Ankyrin 1.

Bioassay-guided isolation of the extract from the marine sponge showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides (-) and eight norsesterterpene cyclic peroxides (-). Among these, 10 (-, , , -) are unprecedented analogs. Compounds with either a hydroxy (, ) or a methoxy (, ) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds , , , and are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds -. The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid displaying the most potent activity (IC 2.0 μM).