The proposed research is to execute the total enantioselective synthesis of four novel strereoisomeric decahydroquinoline alkaloids. Two of the target alkaloids have been isolated from poison frogs and two from leaf- cutter ants. The total synthesis will serve to establish the absolute configuration and structure of these compounds. The synthetic decahydroquinoline alkaloids will be screened in vitro as potential nicotinic acetylcholine receptor-ion channel blockers. Compounds will be evaluated in nicotinic acetylcholine receptor-ion channels in torpedo electrical organ membrane (alpha2betadeltagamma) assays and in rat-brain tissue (alpha4beta2) assays in collaboration with researchers at the UCLA-Harbor Medical Center and the University of Miami.
|Cararas, Shaine A; Izenwasser, Sari; Wade, Dean et al. (2011) Further structure-activity relationship studies on 8-substituted-3-[2-(diarylmethoxyethylidenyl)]-8-azabicyclo[3.2.1]octane derivatives at monoamine transporters. Bioorg Med Chem 19:7551-8|