Solution-Phase Parallel Synthesis of N-Arylisoquinuclidines

The naturally-occurring alkaloid ibogaine, found in the West African shrub Tabernanthe iboga, possesses the ability to diminish self-administration of substances of abuse, such as cocaine, heroin and alcohol. The presence of the isoquinuclidine ring system in the structure of ibogaine became the lead for the design of a 16-member library of N-aryl isoquinuclidines, where pyridine, pyrimidine and quinoline ring systems were attached directly to the bicyclic nitrogen. A solution-phase method for their synthesis is described.