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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Pain relief Pain management New analgesics Pain treatment Drug discovery Drug development Pharmaceutical research Medicinal chemistry New drugs Drug design Synthetic chemistry Chemical synthesis Organic synthesis Molecule synthesis Chemical methods Drug synthesis Salvinorin a research Kor activation Kappa opioid receptor Salvinorin-like compounds Hallucinogenic compounds |
| Key findings | 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.