Designing of Linkers and Solid-phase Oligosaccharide Synthesis by Silver-assisted Gold-catalyzed Glycosidations

Abstract

Carbohydrates are the most abundant biopolymers on the earth and part of every living organism. Unlike nucleic acids and peptides, carbohydrates are more complex and diverse in their structure is one of the main reasons for the slow advancement of glycoscience. Moreover, their isolation from natural sources is also challenging and typically obtained in small amounts as microheterogeneous mixtures. For the synthesis of glycans, several investigators have well-explored chemical and chemo-enzymatic and solid-phase approaches concerning a variety of synthetic methods. Later on, in 2001, Seeberger and coworkers came up with automation in the field of glycomics named “Automated Solid-phase Oligosaccharide Synthesis.” The principal requirement of solid phase chemistry is the compatibility of the three main components (solid support, linker, and reaction condition) employed to carry out the desired synthesis. Merrifield polystyrene resin is the most widely used solid support. Various linkers, such as metathesis cleavable linkers, base labile linkers, and photo-cleavable linkers, have been found suitable for synthesizing oligosaccharides. Oligosaccharide synthesis involves an unavoidable glycosylation reaction that demands different activators in the presence of a glycosyl donor and glycosyl acceptor. The appropriate choice of the glycosylation method, solid support, and linker is the first demand for solid-phase oligosaccharide synthesis (SPOS). In my Ph.D. work, I have put my primary efforts into synthesizing novel linkers, including olefin metathesis and photocleavable linkers, that are useful for SPOS. Furthermore, I have also developed the silver-assisted gold-catalyzed glycosylation protocol on solid supports using these synthesized linkers on Merrifield resin.