A Protecting-Group-Free Synthesis of (-)-Salvinorin A.
Patrick Zimdars, Yuzhou Wang, Peter Metz
Chemistry - A European Journal May 20, 2021 DOI: 10.1002/chem.202100560 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Keywords | Asymmetric catalysis Cycloaddition Mitsunobu reaction Terpenoids Total synthesis |
| Key points | Reports a 16-step enantioselective total synthesis of (-)-salvinorin A from 3-furaldehyde in 1.4% overall yield, using catalytic asymmetric propargylation to set C-12, substrate control for the other six stereocenters, two intramolecular Diels-Alder reactions for the tricyclic core, and a chemoselective Mitsunobu inversion of a syn 1,2-diol that shortened the route by two steps. An alternative intramolecular Diels-Alder strategy with a 2-bromo-1,3-diene was also investigated. |
Abstract
A concise enantioselective total synthesis of the neoclerodane diterpene (-)-salvinorin A is reported. The stereogenic center at C-12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two intramolecular Diels-Alder reactions were applied to generate the tricyclic core. A chemoselective Mitsunobu inversion of a syn 1,2-diol allowed for further streamlining of the original reaction sequence by two steps. Overall, (-)-salvinorin A was synthesized in only 16 steps starting from 3-furaldehyde with 1.4 % total yield. Furthermore, an alternative intramolecular Diels-Alder strategy employing a 2-bromo-1,3-diene moiety was investigated.
Citations in the library
Cited by 5
- An Overview of Syntheses of Salvinorin A and its Analogues ChemCatChem August 26, 2024
- Formal Synthesis of (±)-Salvinorin A via Gold(I) Catalysis. Chemistry - A European Journal September 1, 2023
- A Route to Potent, Selective, and Biased Salvinorin Chemical Space. ACS Central Science August 23, 2023
- Formal Total Synthesis of Salvinorin A ChemistryOpen October 26, 2022
- A route to potent, selective and biased salvinorin chemical space
Cites 30
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin, a new trans-neoclerodane diterpene from Salvia divinorum(Labiatae) Journal of the Chemical Society Perkin Transactions 1 1982
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum The Journal of Organic Chemistry November 1, 1984
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
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