Hetero-Michael addition on a chiral β -amino α,β-unsaturated ketone gave, after some structural modifications, β,β -diamino ketals. Mannich-type reactions of these diamines with an aldehyde led, with high diastereoselectivity, to trisubstituted piperidines. Another highly stereoselective Mannich cyclization, with an N-acyliminium ion generated in situ from the corresponding imide, allowed the preparation of original polycyclic bispidine derivatives. The antinociceptive effect of the three compounds prepared was evaluated in vivo by using the writhing test. If the biological results for the analgesic properties were disappointing, compared with the bispidine HZ2, which has a high affinity for opioid receptors, the modularity of the approach offered the possibility of introducing many substituents for new applications, which was promising because the bispidine core has been described to have many different activities.