The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at alpha4beta2 and alpha7 neuronal nicotinic acetylcholine receptors

Epiboxidine hydrochlorides (+)-2 and (-)-2, which are the structural analogues 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 ?4?2 and ?7 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 unnantural epibatidine enantiomers at the same investigated receptors subtypes.