Natural phosphoglycans containing glycosyl phosphate units: structural diversity and chemical synthesis

Recent Progress in the Synthesis of Glycosyl Phosphate Derivatives

“…agent and condensation with alcohols would give the desired products 12. However, it has been reported that the yields of the products obtained by such reactions are generally low owing to the slowness of the reaction and the presence of side reactions such as those between the hydroxy group of sugars and the condensing agent (1,26). Moreover, the active intermediate 11 is prone to decomposition via an elimination and/or nucleophilic substitution at the anomeric position owing to the leaving ability of the anomeric phosphate group enhanced by the activation.…”

“…Phosphoglycans consisting of glycosyl phosphate repeating units are found in capsular polysaccharides (CPSs) and cell-wall lipopolysaccharides (LPSs) of bacteria, cellwall and extracellular polysaccharides of yeasts, and surface glycocalyx and secreted glycoproteins of protozoan parasites (1). Because these polysaccharides and glycoconjugates define the immunological specificity of the parent microorganism, the primary constituent phosphoglycans have been studied as potential vaccines, particularly against virulent species such as Neisseria meningitidis, Streptococcus pneumoniae, and Leishmania ( Fig.…”

“…Furthermore, the CPSs of bacteria as well as the glycocalyx and secreted glycoproteins of parasites play important roles in infection and the evasion of the host innate defense, contributing to the virulence of these microorganisms. For this reason, the structure-activity relationship and biosynthesis of these polysaccharides and glycoconjugates have also been important subjects of research (1,(6)(7)(8). In addition, glycosyl phosphates are the primary constituents of glycosyl donors in the biosynthesis of carbohydrates, such as sugar nucleotides (9,10) and dolichol phosphate sugars (11,12).…”

“…Chemically modified analogs of these glycosyl donors are used as probes and inhibitors against the biosynthetic pathways of the oligosaccharides (15,16). Chemically synthesized glycosyl phosphate derivatives have become indispensable for all of these studies (1,4,5,8,10). Chemical synthesis of biomolecules is generally advantageous over methods using isolation of those from living organisms in terms of producing sufficient quantities of pure compounds at low costs.…”

“…The availability of chemically modified analogs is another advantage of the chemical synthesis. Such chemical modifications can also be used to develop the aforementioned probes and inhibitors as well as to improve molecular properties such as physicochemical and biological stabilities (1,5).…”