Core Modification of Cytisine: A Modular Synthesis

Getting down to the core: A novel, modular, and more robust synthesis of cytisine, a partial agonist selective for the α4β2 nicotinic acetylcholine receptor, also allows modification of the core structure, as exemplified by the first azacytisine and a cytisine–varenicline hybrid. Key steps include Stille coupling of heteroarylstannanes with a bromolactam motif and an in situ epimerization/alkylative cyclization to complete the tricyclic core (see scheme).