10-step Synthesis of 20-nor-Salvinorin A by Dynamic Strategic Bond Analysis
Jeremy J Roach, Yusuke Sasano, Cullen L. Schmid, Saheem A. Zaidi, Vsevolod Katritch, Raymond C. Stevens, Laura M Bohn, Ryan A Shenvi
ChemRxiv August 19, 2017 preprint DOI: 10.26434/chemrxiv.5318188.v2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper |
|---|---|
| Topics | Salvia divinorum |
| Key points | Deleting the C20 group from salvinorin A stabilizes the molecule, simplifies its synthesis to 10 steps, and retains high affinity and selectivity for the kappa-opioid receptor, enabling further modification of the scaffold. |
Abstract
Salvinorin A (SalA) is a plant metabolite that agonizes the human kappa -opioid receptor (κ-OR) with high affinity and high selectivity over mu- and delta- opioid receptors. Its therapeutic potential has stimulated extensive semi-synthetic studies and total synthesis campaigns. However, structural modification of SalA has been complicated by its instability, and efficient total synthesis has been frustrated by its dense, complex architecture. Treatment of strategic bonds in SalA as dynamic and dependent on structural perturbation enabled the identification of an efficient retrosynthetic pathway. Here we show that deletion of C20 simultaneously stabilizes the SalA skeleton, simplifies its synthesis and retains its high affinity and selectivity for the κ-OR. The resulting 10-step synthesis now opens the SalA scaffold to deep-seated property modification.
Comparable studies
Other theoretical and historical papers on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. | 2008 | Theoretical or philosophical paper | |
| The claustrum's proposed role in consciousness is supported by the effect and target localization of Salvia divinorum. | 2014 | Theoretical or philosophical paper | |
| Total Synthesis of (-)-Salvinorin A. | 2016 | Theoretical or philosophical paper | |
| Salvia Divinorum: entrSalvia divinorum: Entre la prohibición y la construcción de su conocimientoe a proibição e a construção do seu saber | 2022 | Theoretical or philosophical paper | |
| Salvia divinorum induces body awareness changes comparable to metamorphic symptoms in the Alice in Wonderland syndrome | 2019 | Theoretical or philosophical paper |