A new synthetic access to bicyclic iminosugars—derivatives of polyhydroxy decahydropyrido[1,2-a]azepine

Abstract

An efficient and highly stereoselective synthesis of bicyclic iminosugars, derivatives of polyhydroxylated decahydropyrido[1,2-a]azepine, was developed. Starting from a two-component coupling reaction, through nitrone formation and a 1,3 dipolar cycloaddition, an azabicyclic intermediate was obtained. In subsequent reaction sequences, the azabicyclic intermediate was converted into the corresponding epoxide derivative. The N–O bond reductive cleavage, followed by an intramolecular 7-endo-tet cyclization, was the crucial step leading to seven-membered ring closure. Additionally, an alternative synthetic pathway using the bicyclic iodide derivative was explored. The inhibitory activity of the synthesized decahydropyrido[1,2-a]azepines against selected glycosidases was examined.