Synthesis of a cytisine/epibatidine hybrid a radical approach

With the aim of developing a new ligand of neuronal nicotinic receptors (nAChRs) ionic and radical routes to the synthesis of a cytisine/epibatidine hybrid were studied The key step of the convergent synthesis was an unprecedented intramolecular coupling between a primary radical and a pyridine heterocycle The target compound 6 11-diaza was formed with its 4 11-diaza regioisomer (611 ''/411 '' 70/30) Both compounds exhibited a nanomolar affinity at the alpha(4)beta(2) nAChR subtype slightly better for the unexpected regioisomer [K-1 (nM) target compound and its regiolsomer 3 5 and 0 5 nM respectively] (C) 2010 Elsevier Ltd All rights reserved