MDMA (3,4-methylenedioxy-N-methylamphetamine) known on the street as “Ecstasy”, “Adam”, “XTC”, “hug”, “beans”, and “love drug”, is an illegal class A synthetic drug structurally similar to methamphetamine or “crystal meth” that acts as a stimulant and psychedelic. Consumption of “Ecstasy” by humans can lead to severe adverse effects including development of hyperthermia, hallucinations, organ failure and in extreme cases, death. Cognitive impairment has also been reported in “Ecstasy” users and there is evidence that the drug has addictive properties.

Nantenine is a naturally occurring aporphine alkaloid isolated from the Japanese fruit of Nandina domestica. Nantenine has been shown to block and/or reverse behavioral and physiological effects of MDMA in mice. A large body of literature evidence indicates that behavioral and physiological effects of MDMA are mediated by the 5-HT2A receptor and (+) nantenine has been shown to antagonize this receptor. In order to further evaluate the anti-MDMA effects of nantenine in animal models, a good supply of the compound is required and thus a high-yielding synthetic route to the compound is desirable. Additionally, synthesis of nantenine will allow for the preparation of structural analogs which will be useful for evaluating structure-activity relationships at the 5-HT2A receptor.

We have synthesized nantenine in 0.1 %yield using a PIFA-mediated oxidative cyclization as a key step. We will present findings on the synthesis of nantenine as well as our attempts at optimizing the synthetic route.