From common sugars to high value polyhydroxylated compounds: inositols, iminosugars and glycoconjugated azodyes

The object of this Ph. D. thesis is the synthesis of compounds able to mimic saccharide containing natural structures. In particular this topic was developed in three different fields presented here in three sections. In the first one, divided into three chapters, is described the preparation of inositols and some derivatives thereof starting both from methyl beta-D-galactopyranoside or from lactose. The strategy is based first on the preparation of aldohexos-5-ulose derivatives as key intermediates, through a C-5 regioselective oxidation, followed by an intramolecular aldol cyclization which led to inositol derivatives after final reduction of intermediate inososes. The stereochemical outcome of the condensation as well as scope and limitations of this approach have been analysed. Moreover, the possibility to use inositols, where the ring oxygen atom is replaced by a hydroxy-methylene group, as sugar mimics of enhanced stability has been investigated as an innovative application of this section. Chapter four is related to the immune system activation and, in particular, to its innate part where natural killer (NK) cells represent an important protection against pathogenic agents. Recently, some structural features of saccharidic compounds able to activate NK cells have been determined and, starting from lactose and avoiding thus glycosylation steps, two new compounds, beta-D-ManNAc-(1-->4)-D-Glc and beta-D-TalNAc-(1-->4)-D-Glc, have been prepared and tested with interesting results. In this area we studied the preparation of new possible NK activating candidates replacing the gluco-reducing unit with a 1-deoxy-nojirimicin one. In our pathway we chose again commercially available lactose as cheap precursor and hypothesised to modify both its monosaccharide constituents. The galacto portion has to be stereoselectively converted into a 2-N-acetyl-2-deoxy hexosamine unit while the gluco one has to be oxidised in position 5 and then submitted to double reductive amination. This strategy has been entirely developed only for the talosamine series and in this case also using mono protected ethylendiamine in the aminocyclization reaction obtaining a building block for the synthesis of glycodendrimers. The loading on a first generation PAMAM has been performed and will allow us to verify, after deprotection, the biological effects of this multi-presentation. For the GalNAc series a not yet reported approach of 2’ amination with retention of configuration, achieved through a double inversion sequence, has been studied and has been performed also on a monosaccharide derivative. In both cases the target compounds have been obtained in excellent yield and complete stereoselection. Furthermore, the preparation of protected beta-D-ManNAc-(1-->4)-D-Glc has been optimized. In chapter five, section three, is described the synthesis of a new kind of dyes for the textile industry: Glycoazodyes (GADs). The aim of this work was to verify the possibility to reduce the environmental problems connected with the number of different dyes, surfactants, mordants and other pollutants currently used. Our idea took place looking to the structure of some natural water soluble dyes where a saccharide portion is linked to the chromophore. This suggested us to take advantages from the values of both classes of dyes: the large availability of disperse synthetic azodyes and the higher hydrophilic behaviour of natural dyes. The strategy consisted of linking a saccharide from natural renewable sources, such as lactose, D-glucose or D-galactose, to a synthetic dye, a disperse azodye, through a bifunctional linker. Tintorial tests for the first family of GADs, diesteric junction, and for the second family, dietheric junction, revealed very interesting properties. As expected they were more soluble in water, in particular, they didn’t require any auxiliary chemicals during the dye process and they were multipurpose that means that they were able to dye different fabrics.