Biosynthesis of an Anti-Addiction Agent from the Iboga Plant.
Scott C. Farrow, Mohamed O. Kamileen, Lorenzo Caputi, Kate Bussey, Julia E. A. Mundy, Rory C. Mcatee, Corey R. J. Stephenson, Sarah E O'Connor
Journal of the American Chemical Society August 21, 2019 DOI: 10.1021/jacs.9b05999 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Addiction Ibogaine |
| Keywords | Substance abuse treatment Anti-addiction agents Opioid dependence solutions Biocatalysis: biocatalytic synthesis Enzymatic synthesis Chemical synthesis Drug production Pharmaceutical manufacturing Organic chemistry Diels-alder reaction Ibogaine: voacangine Psychoactive compounds Plant-derived drugs Natural products |
| Citations | 69 |
| Key points | Reports the complete biosynthesis of (-)-voacangine and a biocatalytic route to (-)-ibogaine, and notes the opposite enantiomeric configuration of these compounds relative to other major alkaloids in the class. |
Abstract
(-)-Ibogaine and (-)-voacangine are plant derived psychoactives that show promise as treatments for opioid addiction. However, these compounds are produced by hard to source plants, making these chemicals difficult for broad-scale use. Here we report the complete biosynthesis of (-)-voacangine, and de-esterified voacangine, which is converted to (-)-ibogaine by heating, enabling biocatalytic production of these compounds. Notably, (-)-ibogaine and (-)-voacangine are of the opposite enantiomeric configuration compared to the other major alkaloids found in this natural product class. Therefore, this discovery provides insight into enantioselective enzymatic formal Diels-Alder reactions.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Reports the complete biosynthesis of voacangine and a biocatalytic route to ibogaine, noting these compounds show promise as opioid addiction treatments but are difficult to source.
Synthesized
Comparable studies
Other theoretical and historical papers on ibogaine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction. Humans | 2006 | Theoretical or philosophical paper | |
| Ibogaine therapy in the treatment of opiate dependency | 2010 | Theoretical or philosophical paper | |
| On Addiction, Complexity, and Freedom: Toward a Liberation-Focused Addiction Treatment. | 2019 | Theoretical or philosophical paper | |
| The Need for Ibogaine in Drug and Alcohol Addiction Treatment | 2011 | Theoretical or philosophical paper |
Citations in the library
Cited by 6
- Efficient and modular synthesis of ibogaine and related alkaloids. Nature Chemistry March 1, 2025
- Spatiotemporal Mapping of Online Interest in Cannabis and Popular Psychedelics before and during the COVID-19 Pandemic in Poland International Journal of Environmental Research and Public Health May 29, 2022
- New frontiers in the biosynthesis of psychoactive specialized metabolites Current Opinion in Plant Biology September 16, 2024
- The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. Natural Product Reports March 4, 2021
- Voacangine/coronaridine hydroxylases catalyze C19-hydroxylation in iboga alkaloid synthesis. Planta March 23, 2026
and 1 more in the library
Cites 3
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Cytochrome P450 and O-methyltransferase catalyze the final steps in the biosynthesis of the anti-addictive alkaloid ibogaine from Tabernanthe iboga Journal of Biological Chemistry July 20, 2018
- hERG Blockade by Iboga Alkaloids. Cardiovascular toxicology 2016