Glycosidic coupling reactions between two fluorous-tagged D-glucosamine moieties were investigated using several sizes of fluorous tags. The glucosaminyl-glucosamine moiety is found in various bacterial oligosaccharides, although it is more unusual in mammalian systems. Glucosamine presents a certain number of challenges both as a glycosyl donor and as a glycosyl acceptor, including poor reactivity, poor solubility, and limitations in the choice of C2-participating nitrogen protecting groups. D-Glucosamine derivatives bearing different length fluorous amides at the C-2 position, C2F5, C3F7, and C7F15, were synthesized from D-Glucosamine hydrochloride via its 1,3,4,6-O-tetraacetate. Fluorous-tagged glycosyl donors and acceptors were prepared. The trichloroacetimidate of the 3,4,6-O-acetyl-N-perfluoroalkanoyl-D-glycosamine was selected as the glycosyl donor. The glycosyl acceptor was 4,6-O-benzylidene-N-perfluoroalkanoyl-D-glycosamine phenyl thioglycoside, in which the free C-3 hydroxyl group is potentially deactivated by the hydrogen bond from the neighboring amide. Issues of solubility, stereoselectivity, and reactivity were addressed by investigating different combinations of D-glycosamine donors and acceptors with different fluorous tag lengths. Analysis of the coupling reactions was performed by using a 300 MHz NMR. We address whether, in addition to allowing efficient purification of the coupled products, the fluorous tag can act as an efficient C2-participating group, modulate the solubility of the glycosamine precursors, and/or improve the reactivity in the glycosyl coupling reaction. A possible effect of aggregation on the reactivity of these compounds will be discussed.

Possible aggregation effect in fluorous-tagged oligosaccharide synthesis

255th National Meeting (2018)

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