The Efficient Synthesis of Complex-Type N-Glycans

Nagasaki Masahiro, Minamoto Naoya, Shomura Hiroki, Manabe Yoshiyuki, Tanaka Katsunori, Fukase Koichi

doi:10.24496/tennenyuki.57.0_oral45

N-glycans play very unique and important roles in our body, but their functional study is not enough because of complexity and heterogeneity of oligosaccharides in nature. Chemical synthesis of N-glycans is a potent way to more detailed functional study, and we report an efficient synthesis of complex-type N-glycans containing core fucose or bisecting glucosamine, which are related to various vital phenomena and diseases. We have improved some glycosylation steps for efficient glycan synthesis. Microfluidic reaction improved the yield and the stereoselectivity of a-sialylation, b-mannosylation, and N-glycosylation. On the other hand, the problem of low reactivity of disaccharide donor 10 could be solved by converting NAc group at C5 of sialic acid to NAc₂group, which doesn’t form a supramer with intermolecular hydrogen bonding.The whole structure of biantennary N-glycans were constructed by twice glycosylation to branching mannose. Although stereoselectivity was low, (4+4) and (4+8) glycosylation proceeded with high yield in ether solvent to obtain core fucose-containing dodecasaccharide-Asn 20. The problem of stereoselectivity was solved by changing protective group at C4 of mannose of glycosyl donor and bisecting glucosamine-containing octasaccharide-Asn 30 was obtained using the new donor 27. All protective group of protected glycan 20 were removed in 4 steps to finish the synthesis of core fucose-containing N-glycan 23.

The Efficient Synthesis of Complex-Type N-Glycans

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