Chemical syntheses of the salvinorin chemotype of KOR agonist.
Natural product reports November 18, 2020 Sarah J Hill, Aurélien U C M Brion, Ryan A Shenvi
Salvinorin A, a hallucinogenic compound from the plant Salvia divinorum, is a potent and selective activator of the kappa-opioid receptor (KOR), a promising target for new painkillers. Unlike typical opioids, it lacks a basic nitrogen, enters the brain rapidly, and has a short duration of action. Since 2000, extensive medicinal chemistry using semi-synthesis from plant extracts has explored its properties. Total synthesis efforts have produced multiple routes to create salvinorin A and related analogs, aiming to improve its activity for various therapeutic effects. This review covers those total syntheses and identifies remaining challenges for future synthetic chemistry to address.