Automated Solid Phase Oligosaccharide Synthesis

Of the three classes of biopolymers—nucleic acids, proteins and glycoconjugates, nucleic acids and proteins have seen the most breakthroughs in understanding their biological role, in part due to their ready availability. The automation of oligonucleotide and peptide synthesis has been fruitful in providing biologists and biochemists with pure, well-defined structures. This work reviews the recent developments in the automated synthesis of oligosaccharides, the third class of biopolymers. Both glycosyl phosphates and glycosyl trichloroacetimidates have been used successfully in the automated assembly of oligosaccharides employing an octenediol-functionalized polystyrene resin. The product was cleaved either by methanolysis of an ester bond or by olefin cross metathesis. Several biologically important carbohydrates have been synthesized by automation, in a fraction of the time needed to synthesize them by traditional methods. For example, the tumor associated antigens Lewis Y, Le(y)-Le(x), were synthesized by automation. A Leishmania cap tetrasaccharide and a malaria toxin vaccine candidate were also assembled.