Biosynthesis of an Anti-Addiction Agent from the Iboga Plant.
Journal of the American Chemical Society – August 21, 2019
Source: PubMed
Summary
Treatments for opioid addiction could be revolutionized by plant derived psychoactives like (-)-ibogaine and (-)-voacangine, but their natural sources are scarce. Researchers have now achieved the complete biocatalytic production of (-)-voacangine. This breakthrough allows for its conversion to (-)-ibogaine through simple heating, overcoming previous supply challenges. This advance also offers new insights into enantioselective enzymatic formal Diels-Alder reactions, paving the way for more accessible anti-addiction agents.
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.