Simplification of hallucinogen pays off

Abstract

Salvinorin A, a hallucinogen produced by the Mexican plant Salvia divinorum, holds promise for treating itch and pain because it activates the kappa opioid receptor while avoiding the mu opioid receptor, a sister receptor that’s been associated with opioid abuse. Chemists have tried to synthesize salvinorin A so that they could alter the structure to sidestep the compound’s psychoactive effects while preserving its analgesic properties. But salvinorin A’s scaffold has been challenging to recreate. Now, a team of scientists at the California and Florida branches of Scripps Research Institute, as well as at the University of Southern California, report a 10-step total synthesis of 20-norsalvinorin A (ChemRxiv 2017, DOI: 10.26434/chemrxiv.5318188). The compound differs from salvinorin A by a single methyl group and binds to the kappa opioid receptor with an affinity similar to that of the natural product. When given to mice, it also relieves itch. The report is one