A NEW ACCESS TO PIPERIDINO-CYCLOPIPERIDINECARBOXAMIDES - CONSTRAINED ANALOGS OF A PHARMACEUTICAL USED DIAMINIC BUILDING-BLOCK

6-Piperidino-3-azabicyclo [3.1.0]hexane-6-carboxamide diastereomers 1a and 2a represent conformationally rigid analogues of 3a which is a bu ilding block in some pharmaceutical compounds. A new access to these c ompounds 1a and 2a was found via the cleavage of bicyclic N,N-acetal 6 with hydrocyanic acid as the stereodetermining step. Reaction of deri vatives 1a and 2a with bromodiphenyl-butyronitrile 14 gave cyclopiritr amide isomers 1c and 2c, respectively. Qualitative preliminary investi gations showed different affinities of 1c and 2c to the opiate-mu rece ptor. These results were discussed on the basis of an X-ray structural analysis of cyclopiritramide isomer 2c.1-Benzylcyclopiperidine deriva tives 1d and 2d were used as model systems for studying the conformati on of cyclopiritramide isomer 1c and 2c, respectively.