Innovative approaches to access mono- and bicyclic iminosugars: synthesis and biological evaluation

Iminosugars are among the most notable classes of glycomimetics known nowadays Because of their numerous therapeutical applications, these alkaloids continue to receive considerable attention among synthetic chemists. Innovative, stereoselective, and green synthetic routes to mono- and bicydic iminosugars and their biological evaluation towards selected enzymatic targets are described in this project. Because of their ability to resemble the structures of sugars and mimic their conformations, water solubility, high Selectivity towards targets, and stability against processing, iminosugars play a pivotal role among the various inhibitors of carbohydrate- processing enzymes. Due to their potential as drugs for many diseases, developing more efficient ways to synthesize naturally occurring iminosugars with known bioactivity and original routes to novel congeners is the main challenge in this field. As a natural and easily accessible source belonging to the chiral pool, most synthetic procedures utilize carbohydrates as starting materials, which are lately manipulated in various ways to introduce the nitrogen atom. One of the most straightforward strategies to achieve this task is converting a carbonyl compound into a nitrone through condensation with hydroxylamines. The nitrone can be further functionalized and cyclized to final structures employing reductive amination reaction (RA). In this context, the diol 1, easily accessible on a multi-gram scale from inexpensive D- mannose in three steps and already widely used at DICUS to access a variety of polyhydroxypiperidines, can be envisioned as a general precursor of 6- and 7- membered nitrogen heterocycles as well as of bicyclic iminosugars.