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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
A concise synthetic pathway for trans-metanicotine analogues
1College of Pharmacy, Kangwon National University, Chunchon, Korea. haeilp@cc.kangwon.ac.kr
Abstract:
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.
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