Synthesis of Anabaseine and Anabasine Derivatives: Structural Modifications of Possible Nicotinic Agonists

Abstract

Coupling nicotinoyl chloride with 3,4‐dimetoxyphenethylamine under Bischler‐Napieralski cyclization afforded the isoquinoline (4) in good yield. This latter was used as starting material to obtain with only hydrobromic acid a product with demethylation at the position 7 (5). In addition, treatment of (4) with NaBH₄/MeOH gave 6,7‐dimetoxy‐1‐(pyridin‐3‐yl)‐1,2,3,4‐tetrahydroisoquinoline (6) and unexpectedly, under mild reduction of the pyridine moiety with H₂/PtO₂/AcOH/, gave 6,7‐dimetoxy‐1‐(piperidin‐3‐yl)‐1,2,3,4‐tetrahydroisoquinoline (7) as the title compound. The unusual chemical reactivity of 4 onto acidic conditions and catalytic hydrogenation allowed us to obtain anabaseine and anabasine derivatives under mild conditions.

Keywords:

• anabaseine
• anabasine
• 1‐(pyridin‐3‐yl)isoquinoline
• nicotinic acetylcholine receptor

Acknowledgments

E. S. S. thanks FONDECYT Grant No. 1030963 for financial support and B. Cassels for his invaluable help with this research.