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Core Modification of Cytisine: A Modular Synthesis


  • Funding from the Rotary Foundation (to C.H.) and the EPSRC (to C.A.H.) is acknowledged.


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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).