A concise synthetic pathway for trans-metanicotine analogues.
A convenient pathway for synthesis of trans-metanicotine analogues was developed. trans-Metanicotine, a subtype (alpha4beta2)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. Zn-mediated allylation of allyl bromide and acetaldehyde followed by Heck reaction with 3-bromopyridine gave 5-pyridin-3-yl-pent-4-en-3-ol (2). Tosylation of 5-pyridin-3-yl-pent-4-en-3-ol followed by substitution reaction with methylamine in sealed tube gave methyl-(1-methyl-4-pyridin-3-yl-but-3-enyl)-amine (4) in good yields. Thus, trans-metanicotine analogues modified at the alpha-position of the methylamino group with various functional groups can be obtained in 4 steps.
Park
H
H
College of Pharmacy, Kangwon National University, Chunchon, Korea. haeilp@cc.kangwon.ac.kr
Jang
J
J
Sin
K S
KS
D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D018722:Nicotinic Agonists / Q000138:chemical synthesis*
D018722:Nicotinic Agonists; C012419:metanicotine; D009538:Nicotine