Collybolide is a secondary metabolite of the Rhodocollybia maculata mushroom, a basidiomycete fungus that grows on rotting conifer wood.

[1] However, a total synthesis and independent biological assay determined that collybolide neither excites nor suppresses kappa-opioid receptor signaling.

[8] Importantly, early reports were unable to confidently assign the absolute configuration of collybolide; a 1986 isolation of a collybolide congener noted that the absolute configuration of the series "remains to be determined",[9] and a 2001 circular dichroism study was only able to tentatively infer which enantiomer naturally occurred based on density functional theory calculations.

These results attracted widespread attention in the biomedical community, as collybolide appeared to be a potent and selective KOR agonist that might be developed into a new treatment for pain or pruritus,[11][12] lacking the adverse effects of typical mu-opioid receptor agonist pain treatments.

[2][16] Key features of the synthesis included an enantioselective Diels-Alder reaction using the Hayashi-Jørgensen proline organocatalyst, and an enamine [3,3]-sigmatropic rearrangement to stereoselectively install a late-stage benzoyloxy (BzO) group.