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

Abstract

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.