Novel approaches for synthesizing oligosaccharides and glycoconjugates of biological importance
Elsayed, Galal Abdel Megeed
MetadataShow full item record
Glycoconjugates play a major role in inflammation, immune response, metastasis, fertilization, and embryogenesis. A major impediment to the rapidly growing field of molecular glycobiology is the lack of pure, structurally defined oligosaccharides and glycoconjugates. Besides the fact that these molecules are often found only in low concentrations in nature, the identification and isolation of complex carbohydrates from natural sources are greatly complicated by their microheterogeneity. Synthesis is an alternative way to have these molecules but the procurement of synthetic material presents a formidable challenge to synthetic chemists although the steady increasing in recent years for chemically defined oligosaccharides. As an attempt to develop a methodology for the synthesis of oligosaccharide libraries, in this program, a novel approach to synthesize a library of disaccharides using soluble polymeric support is demonstrated. The resin-bound glycosyl acceptors 1, 2, and 3 were glycosylated with a range of glycosyl donors 4, 5, and 6. A library of 18 disaccharides was obtained, six disaccharides in each pot. Each disaccharide was released from the polymer support by selective cleavage of the linkers. In this program, α-D-Mannopyranosylphosphate serine derivatives were conveniently synthesized by reaction of benzyl or cynaoethyl phosphochloroamidite with 2,3,4,6-tetra-O-acetyl-D-mannopyranose to give intermediate α-manopyranosyl phosphoramidites were successively reacted with properly protected serine (as carbamate or imine) derivatives in the presence of 1H-tetrazole to give phosphite triesters which could be oxidized to phosphotriesters using t-BuOOH. It has been shown that the new approach for coupling α-mannosyl phosphoramidite to a range of serine derivatives provides phosphotriester products in good yield and pure α-anomeric selectivity. The best yields were obtained when the imine-protected derivatives of serine were coupled to the phosphoramidite of α-mannose. This approach can be utilized for the phosphoglycosylation of different peptides containing hydroxyl amino acids such as, serine, threonine, tyrosine, or hydroxylysine. Also, it can be employed for the global glycophosohorylation of pre-assembled peptides. The building block approach can be also utilized to synthesize the same phosphoglycopeptide using the appropriate protected mannosyl phosphate serine derivatives such as building block 37.