| Human milk oligosaccharides are the third largest substance in breast milk after lactose and lipids,and have important nutritional value and extensive biological functions.Studies have shown that it has physiological activities such as resisting pathogen infection,regulating intestinal microecology,regulating immune system and antiviral.In nature,the clustering effect of multivalent substrates is an effective way to achieve enhanced binding between ligands and receptors in biological systems.In order to study the action mechanism and active function of human milk oligosaccharides with specific structure,the preparation of human milk oligosaccharide trisaccharide 2’-fucosylated lactose(2’-FL),3-fucosylated lactose(3-FL)and their polyvalent glycopolymers were explored.The human milk oligosaccharide trisaccharides 2’-FL and 3-FL are two fucosylated oligosaccharides with high concentrations in breast milk.It has the function of soluble receptor analog effect of mutual recognition between epithelial cells and pathogens,which can act as competitive bait for intestinal pathogens and inhibit the infection of intestinal epithelial cells.In this paper,the human milk oligosaccharide trisaccharides 2’-FL and 3-FL were prepared,and the effective methods of preparing its derivatives were also explored.For the preparation of 2’-FL,lactose was used as the raw material,and α-fucosyl was introduced at the 2’-position through a stereoselective glycosylation reaction after the regioselective protection of propylidene and pivaloyl groups.After a two-step deprotection reaction,human milk oligosaccharide trisaccharides 2’-FL was obtained.The yield of each step was between 50%-90%,and the total yield was 25%.For the preparation of 3-FL,glucose was used as the raw material,and the α-fucosyl group was stereoselectively introduced at the 3-position after protecting the 4,6-position hydroxybenzylidene group.After debenzylidene and selective acyl protection,introduce β-galactosyl by glycosylation at 4-position.After a series of deprotection reactions,human milk oligosaccharide trisaccharides 3-FL was obtained.The yield of each step was between 30%-98%,and the total yield was 14%.The functionalized 2’-FL and 3-FL derivatives were prepared.A hydrophilic polyether linker was introduced by activation of the anomeric carbon position of the trisaccharide.After a series of functional group transfermation reactions,two kinds of human milk oligosaccharide trisaccharides polymer monomers were prepared.The yield of each step in the series of reactions was between 20%-70%.The total reaction yield of 2’-FL polymerized monomer was 1.5%,and the total reaction yield of 3-FL polymerized monomer was 2.7%.2’-FL and 3-FL functional derivatives were prepared.2’-FL glycopolymer with polymerization degree of 120 and 3-FL glycopolymer with polymerization degree of 90 were obtained by RAFT polymerization in a control manner at the ratio of sugar monomer: chain transfer agent: initiator = 200:1:0.5.In this paper,polyvalent galactosyl and fucosyl glycopolymer were designed and prepared in the same way.It can be used as a natural ligand control derivative for donor-acceptor binding.In the series of derivatization reactions,the yield of each step was between 40%-90%.The degree of polymerization of the final product galactosyl glycopolymer and fucosyl glycopolymer was 142 and 170,respectively.The oligosaccharides prepared in this paper are all more than 95% pure.The structure was characterized by nuclear magnetic resonance and high performance liquid chromatography-mass spectrometry.The series of human milk oligosaccharide polymers prepared in this paper provide a material basis for studying the specific recognition and action mechanism of human milk oligosaccharide in biological system.Studying the metabolic mechanism of human milk oligosaccharide in vivo can provide theoretical basis for developing functional products,which can help with the promotion of national nutrition levels and promote the development of food industries in the future. |
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