Stereocontrolled synthesis of pyrrolidine iminosugars through asymmetric dihydroxylation of optically active olefins

Iminosugars, carbohydrate analogues in which the endocyclic oxygen is replaced by a nitrogen atom, are nowadays the most attractive class of sugar mimics because of their high glycosidase and glycosyltransferase inhibitor activity and hence their therapeutic potential in a vast array of diseases, such as diabetes, glycosphingolipid storage disorders and viral infections (HIV, hepatitis Band C). In our approach for preparation of some classes of iminosugars, the synthetic key step is the asymmetric dihydroxylation reaction (AD). Recently we conducted a systematic study about AD reaction on the unsaturated azido alchohols identified in our precedent studies as the ideal precursors of pyrrolidine ring. The conditions were optimized in order to modulate the diastereomeric ratio of the diols depending on which Cinchona type chiral ligand was used, thus allowing to obtain four adjacent stereocentres with full stereochemistry control. Once we have the triols, we have proceeded the synthesis of respective iminosugars.