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.