Disrupting Substance Use Disorder: The Chemistry of Iboga Alkaloids.

Iboga alkaloids, natural compounds from the Tabernanthe iboga plant, include ibogaine, which reduces self-administration of opiates, amphetamines, alcohol, and nicotine in rodents. Despite its promise for treating substance use disorder, ibogaine is suboptimal for human use due to cardiotoxicity and hallucinogenic effects, making it a lead for drug development. Over twenty total syntheses of ibogamine, ibogaine, and close relatives exist, but fewer for recently isolated iboga alkaloids. This review covers synthetic strategies for both classical and non-classical iboga alkaloids.

Study at a glance

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.