Synthesis And Glycosidase Inhibition Of Polyhydroxylated Azepane Derivatives

Iminosugars, which are efficient inhibitors of glycosidases, have important pharmacologic activities. The molecular skeletons of naturally occurring iminosugars only contain five-and six-membered rings. As their higher homologues, polyhydroxylated azepanes (azepane iminosugars) show considerable bioactivities but are investigated relatively less. We hope to develop general methods to prepare polyhydroxylated azepanes derivatives, to study their structure-activity relationship and glycosidase Inhibition. This thesis is devided into two parts:1) With D-mannitol and D-gluctiotol as starting materials, polyhydroxylated azepanes was developed with double SN2 reaction or nucleophilic addition with plus nitrogen as key steps. The corresponding N, N-dialkyl derivatives were also obtained for studies on their glycosidase inhibition.2) Novel iminosugar skeletons were constructed based on the azepane ring contraction strategy. D-mannose derived azepane 146, which has diversely protected hydroxyl groups, is an important precursor. By intramolecular SN2 reaction of 146, ring contraction was successfully realized to afford novel polyhydroxylated azepanes derivatives.