Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids.

Summary

Ibogaine, a major alkaloid from the root of Tabernanthe iboga, shows promise for treating substance use disorders due to its ability to reduce self-administration of various substances in rodents. However, it is not optimal for human treatment because of its cardiotoxicity and hallucinogenic effects. The review discusses synthetic strategies for both classical and recently isolated iboga alkaloids, noting that while over twenty total syntheses of ibogaine and related compounds exist, fewer have been conducted for new alkaloids.

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Abstract

The iboga alkaloids are a family of monoterpene indole alkaloids first discovered from the root of Tabernanthe iboga. The major alkaloid constituent in the root, ibogaine, has garnered interest for its anti-addictive properties. Ibogaine has been shown to reduce opiate, amphetamine, alcohol, and nicotine self-administration in rodents. However, ibogaine itself is less than optimal as a treatment in humans for Substance Abuse Disorder (SUD) due to its cardiotoxicity and hallucinogenic potential. Instead, ibogaine is an attractive lead for drug discovery efforts. Indeed, several notable programs have been launched to both elucidate ibogaine's mechanism of action and reduce its toxicity. While there have been over twenty total syntheses of ibogamine, ibogaine, and closely related family members, there are far fewer syntheses of recently isolated iboga alkaloids. In this targeted review, we discuss the synthetic strategies applied to the synthesis of classical and non-classical iboga alkaloids.

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