Highly Stereocontrolled De Novo Synthesis of N-Alkyl L-Deoxynojirimycin Derivatives and their Pharmacological Applications In Rare Diseases

Over the years, the interest for the synthesis and pharmacological behavior of iminosugars, sugar analogues in which the endocyclic oxygen of carbohydrate is replaced by an imino function, has greatly grown up. Despite their wide therapeutic potential, iminosugars and their N-alkylated congeners suffer of poor in vivo selectivity1 hampering their long-term medical applications. On the other hand, L-iminosugars have displayed in several contexts more efficient pharmacological properties than their D-antipodes toward specific enzymes, acting either as inhibitors or activators.2 Inspired by these observations, we have first tuned up a synthetic strategy to prepare enantiomerically pure L-DNJ3, i.e. L-deoxynojirimycin (to the best of our knowledge never reported before) and then we have developed an alternative route to the existing methods for N-alkylation of iminosugars and alkyl chains assembly. Particularly, L-DNJ was prepared by a stereocontrolled de novo method4 starting by the synthetically available enol thioether 1 and the Garner aldehyde 2