The Enantiomers Of Epiboxidine And Of Two Related Analogs: Synthesis And Estimation Of Their Binding Affinity At Alpha 4 Beta 2 And Alpha 7 Neuronal Nicotinic Acetylcholine Receptors

Epiboxidine hydrochlorides (+)-2 and (-)-2, which are the structural analogs of the antipodes of epibatidine (+/-)-1, as well as the enantiomeric pairs (+)-3/(-)-3 and (+)-4/(-)-4 were synthesized and tested for binding affinity at a4 beta 2 and a7 nicotinic acetylcholine receptor (nAChR) subtypes. Final derivatives were prepared through the condensation of racemic N-Boc-7-azabicyclo[2.2.1]heptane-2-one (+/-)-5 with the resolving agent (R)-(+)-2-methyl-2-propanesulfinamide. The pharmacological analysis carried out on the three new enantiomeric pairs evidenced an overall negligible degree of enantioselectivity at both nAChRs subtypes, a result similar to that reported for both natural and unnatural epibatidine enantiomers at the same investigated receptor subtypes. Chirality 24:5435-51, 2012. (C) 2012 Wiley Periodicals, Inc.