Synthesis, structural and conformational study of some esters derived from 3-methyl-3-azabicyclo[3.2.1]octan-8(α and β)-ols

6 pags.; 1 sch.; 4 tabs.A series of α and β-esters bearing a 3-methyl-3-azabicyclo[3.2.1]octane moiety as well as methyl and aryl substituents were synthesized and studied by 1H and 13C NMR spectroscopies. In CDCl3 solution, at room temperature, a chair-envelope conformation for the bicycle moiety with the N-CH3 group in equatorial position with respect to the chair ring is proposed for both, α and β-esters. The chair conformation of the piperidine ring is puckered at C8 in the α-epimers and it is flattened at N3, in the β-epimers. Free rotation of the acyloxy group around the C8O bond has also been deduced. Analgesic activity of four of these substances was studied. 8β-Benzoyloxy-3-methyl-3-azabicyclo[3.2.1]octane demonstrated significant analgesic activity in the hot plate test compared to morphine. By measuring the rectal temperature in mice, results also showed a significant antipyretic activity of this compound.The authors thank A. Madrid for the synthesis of the compounds. They also thank Dr. A. Orjales (FAES S.A. Laboratories, Bilbao, Spain) the pharmacological data.Peer Reviewe