Salvaging Salvinorin: From Hallucinogen to Potential Therapeutic through Chemical Synthesis
ACS Central Science August 10, 2023 Bhawyanth Duvvuru, Myles W. Smith
Salvinorin A (SalA), the most potent naturally occurring hallucinogen, is a polycyclic terpenoid from Salvia divinorum that acts as a selective kappa-opioid receptor (KOR) agonist, a target for non-addictive analgesics. Its complex structure limits synthetic modifications. In this work, Shenvi, Bohn, and co-workers developed a concise synthetic route to SalA analogues that overcome the natural compound's liabilities, yielding compounds with improved activity, KOR-selectivity, and functional bias. This approach offers new opportunities for exploring KOR-selective compounds, which avoid the addictive effects associated with mu-opioid receptor activation, potentially addressing the societal burden of opioid abuse.