Functionalization of the alicyclic skeleton of epibatidine: synthesis and nicotinic acetylcholine receptor binding affinities of epibatidine analoguesElectronic supplementary information (ESI) available: detailed experimental procedures with spectroscopic data, and crystal data for compounds 11 and 4a. See http://www.rsc.org/suppdata/ob/b3/b308906a/Dedicated to Dr John W. Daly of the NIH, who first discovered epibatidine.

Abstract

A novel method for the epimerization of endo-2-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptan-3-one (12) on silica gel was developed and used as the key step to synthesize functionalized analogues of epibatidine which were evaluated for their nicotine receptor subtype selectivity in binding studies.