A Review of the Organic Synthesis and Medicinal Applications of the Natural Product Cytisine

Cytisine (CYT) is a naturally occurring chiral alkaloid which is known to be a ligand of nicotinic acetylcholinergic receptors (nAChRs). This compound has been a subject of quite intensive pharmacological research to explore CYT impact on the nAChRs. CYT may be a both more clinically effective and more cost-effective smoking cessation aid than varenicline (the most effective, but most expensive smoking cessation medication currently available), which belongs to the same category of agonists. Several strategies have been developed for the synthesis of CYT and its derivatives. Herein we review the strategies that have been employed for the synthetic formation of the tricyclic CYT molecule. Synthetic approaches include the formation of (±)-CYT from bipyridines, synthesis of (+)-CYT using chiral pools and the use of microorganisms to synthesize (-)-CYT. Due to the clinical importance of CYT, we hope a review of synthetic pathways may advance research into CYT.