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 via PubMed
Summary
AI-generated from the abstractThe plant-derived psychoactive compounds (-)-ibogaine and (-)-voacangine show promise for treating opioid addiction but are difficult to obtain from natural sources. Researchers achieved the complete biosynthesis of (-)-voacangine and its de-esterified form, which converts to (-)-ibogaine upon heating, enabling biocatalytic production. These compounds have the opposite enantiomeric configuration compared to other major alkaloids in their class, offering insight into enantioselective enzymatic formal Diels-Alder reactions.
Study at a glance
| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Keywords | Substance abuse treatment Anti-addiction agents Opioid dependence solutions Biocatalysis: biocatalytic synthesis Enzymatic synthesis |
| Citations | 69 |
| Key finding | Complete biosynthesis of (-)-voacangine and its conversion to (-)-ibogaine enables biocatalytic production of these opioid addiction treatment candidates. |
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.