SYNTHESIS OF GLYCOSIDASE INHIBITORS BASED ON BICYCLIC AZETIDINES FOR THE TREATMENT OF CANCER

摘要

Iminosugars are medically relevant sugar analogues with powerful biological activity, in most cases due to their inhibition of glycoside processing enzymes. Thus, they are promising medicines for the treatment of a broad spectrum of diseases and disorders. In particular, the natural occurring iminosugar castanospermine is a potent inhibitor of α-glucosidases, and has been found to exhibit antitumoral and antiviral activity, however it lacks selectivity. A series of ring contracted castanospermine analogues has been synthesised from L-arabinose. The four-membered azetidine ring system was accessed by a key ditriflate displacement reaction. Subsequently, chain extension via a Wittig reaction allowed formation of the desired bycyclic system.