O6C-20-nor-salvinorin A is a stable and potent KOR agonist.
Shun Hirasawa, Min Cho, Tarsis F. Brust, Jeremy J Roach, Laura M Bohn, Ryan A Shenvi
Bioorganic & Medicinal Chemistry Letters September 1, 2018 DOI: 10.1016/j.bmcl.2018.01.055 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Conformational analysis Heck reaction Kappa opioid receptor Total synthesis |
| Key points | Replacing C20 with H and O6 with CH2 in Salvinorin A yields a compound, O6C-20-nor-SalA, that is stable against C8 epimerization and retains high KOR agonism potency. |
Abstract
Salvinorin A (SalA) is a potent and selective agonist of the kappa-opioid receptor (KOR), but its instability has frustrated medicinal chemistry efforts. Treatment of SalA with weak bases like DBU leads to C8 epimerization with loss of receptor affinity and signaling potency. Here we show that replacement of C20 with H and replacement of O6 with CH2 stabilizes the SalA scaffold relative to its C8 epimer, so much so that epimerization is completely supressed. This new compound, O6C-20-nor-SalA, retains high potency for agonism of KOR.
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- Salvaging Salvinorin: From Hallucinogen to Potential Therapeutic through Chemical Synthesis ACS Central Science August 10, 2023
- Chemical syntheses of the salvinorin chemotype of KOR agonist. Natural Product Reports November 18, 2020
- A Route to Potent, Selective, and Biased Salvinorin Chemical Space. ACS Central Science August 23, 2023
- A Protecting-Group-Free Synthesis of (-)-Salvinorin A. Chemistry - A European Journal May 20, 2021
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- Dynamic Strategic Bond Analysis Yields a Ten-Step Synthesis of 20-nor-Salvinorin A, a Potent κ-OR Agonist. ACS Central Science December 27, 2017
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