UC Davis

The Iboga alkaloid family of natural products has drawn a lot of attention due to their potential effectiveness for treating substance use disorder. However, their adverse effects including ataxia, nausea, cardiotoxicity, and hallucinations limit their therapeutic potential. Generating non-hallucinogenic analogs of this promising scaffold with increased safety profiles would significantly help combat drug addiction and contribute positively to the current opioid epidemic in America. Current syntheses of ibogaine, which is a member of the family, involve long linear sequences with hash conditions. We are developing a short, modular, and robust synthesis of ibogaine that allows for the rapid generation of structurally diverse analogs. Routes involving key intra- and intermolecular Diels-Alder reactions have both been explored to build the unique isoquinuclidine scaffold of iboga family alkaloids.