Biosynthesis of an Anti-Addiction Agent from the Iboga Plant

• Published in: Journal of the American Chemical Society Vol. 141; no. 33; pp. 12979 - 12983
• Main Authors: Farrow, Scott C, Kamileen, Mohamed O, Caputi, Lorenzo, Bussey, Kate, Mundy, Julia E. A, McAtee, Rory C, Stephenson, Corey R. J, O’Connor, Sarah E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21-08-2019
• Subjects: Communication
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.9b05999

(−)-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.