Updated project metadata. The fused macrocycles and multiple stereocenters of briarane-type diterpenoids pose a major challenge to total synthesis and efforts to characterize their biological activities. Harnessing a scalable source of excavatolide B (excB) from cultured corals, we developed two structurally distinct clickable excB probes that retained the anti-inflammatory biological activities of excB. Here we used these probes in a chemoproteomics strategy to the cellular target(s) of excB in mammalian cells.