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.