Chemical syntheses of the salvinorin chemotype of KOR agonist.
Sarah J Hill, Aurélien U C M Brion, Ryan A Shenvi
Natural product reports November 18, 2020 DOI: 10.1039/d0np00028k via PubMed
Summary
AI-generated from the abstractSalvinorin 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.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Pain relief Pain management New analgesics Pain treatment Drug discovery |
| Key finding | Total syntheses of salvinorin A and its analogs have been achieved via multiple orthogonal routes, but outstanding problems remain for synthesis to address in optimizing activity for therapeutic use. |
Abstract
Covering: 2000 to 2020 The hallucinogenic diterpene salvinorin A potently and selectively agonizes the human kappa-opioid receptor (KOR). Its unique attributes-lack of a basic nitrogen, rapid brain penetrance, short half-life-combined with the potential of KOR as an emerging target for analgesics have stimulated extensive medicinal chemistry based on semi-synthesis from extracts of Salvia divinorum. Total synthesis efforts have delivered multiple, orthogonal routes to salvinorin A, its congeners and related analogs with the goal of optimizing its activity towards multiple functional endpoints. Here we review total syntheses of the salvinorin chemotype and discuss outstanding problems that synthesis can address in the future.