Dottorato in SCIENZE CHIMICHE

Titolo della tesi: Stereocontrolled Total Synthesis of Iminosugars and Their Derivatives with Potential Therapeutic Activities

Iminosugars are polyhydroxylated compounds which differ from the carbohydrates in the presence of the endocyclic nitrogen atom in place of the oxygen. Iminosugars are able to interact with numerous fundamental enzymes by mimicking the sugars, hence, they have tremendous potential applicability as therapeutics in a vast array of disease, such as cancer, diabetes, lysosomal storage disorders and viral infections. The significant biomedical implications of iminosugars has aroused the interest in the research of new strategies aimed at obtaining them. In this work, I report our stereocontrolled total synthetic approach which provides the access to several classes of diastereomeric iminosugars from a common precursor, while controlling the four contiguous stereocenters. The control of the four contiguous stereocenters is achieved through an opportune sequence of stereocontrolled key steps: the asymmetric Sharpless epoxidation, the asymmetric dihydroxylation (or amino hydroxylation), and the epoxide ring opening with suitable nucleophiles. Through the opportune sequence of the key steps listed above, the choice of the chiral ligands and the suitable nucleophiles in the epoxide ring opening, after the optimization of some crucial steps, is possible to obtain a large library of iminosugars and their derivatives, starting from a common precursor. Once obtained, the iminosugars will be tested for their biological activity. Furthermore, the possibility to anchor iminosugars to magnetic nanoparticles will enable further studies regarding their applicability in the drug delivery field.