Aggregation of a Tetrasaccharide Acceptor Observed by NMR: Synthesis of Pentasaccharide Fragments of the Le(a)Le(x) Tumor-Associated Hexasaccharide Antigen.

We report the synthesis of a tetrasaccharide and two pentasaccharide fragments of the Le(a)Le(x) tumor-associated carbohydrate antigen α-L-Fuc-(1→4)-[β-D-Gal-(1→3)]-β-D-GlcNAc-(1→3)-β-D-Gal-(1→4)-[α-L-Fuc-(1→3)]-β-D-GlcNAc-(1→OR). The choice of protecting groups permitted a one-step global deprotection (Na/NH3(l)). The protected chlorohexyl glycoside pentasaccharide was the precursor to the hexyl glycoside, to be used as a soluble inhibitor, and the aminohexyl glycoside analogue, to be conjugated to proteins for surface immobilization and immunization experiments. We observed that a linear tetrasaccharide that contained two N-acetylglucosamine residues and a free OH group gave two distinct sets of (1)H NMR signals when the data were acquired in deuterated chloroform. Data acquisition at variable concentrations and variable temperatures suggests that the second set of NMR signals results from aggregation of the tetrasaccharide driven by the formation of intermolecular H-bonds involving the NHAc. While the formation of intra- and intermolecular H-bonds involving N-acetylgucosamine residues has been reported in non-H-bonding solvents, this is, to our knowledge, the first time that these have lead to the appearance of two distinct sets of signals in the NMR spectra. This aggregation may explain the lack of reactivity observed when an attempt is made to glycosylate such an acceptor using non-H-bonding solvents such as dichloromethane.

Citation

Deng Kuir, Mickaël Guillemineau, France-Isabelle Auzanneau. Aggregation of a Tetrasaccharide Acceptor Observed by NMR: Synthesis of Pentasaccharide Fragments of the Le(a)Le(x) Tumor-Associated Hexasaccharide Antigen. The Journal of organic chemistry. 2015 May 15;80(10):5004-13

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PMID: 25860389

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