We present a versatile carbohydrate ligation technique based on the reaction of cyclic carbamates with primary amines. Cyclic-carbamate-derivatized carbohydrates can be added to primary amine-containing molecules in aqueous or non-aqueous solutions to yield corresponding urea derivatives. This technique was used to attach sugar residues to a wide range of building blocks and biomolecules.
Our group is studying the biochemical and physiological roles of human milk oligosaccharides (HMO) and neoglycoconjugates thereof. Cyclic carbamates of HMOs including lactose, 3’- and 6’-sialyl lactose, 2’- and 3-fucosyl lactose were synthesized from corresponding free oligosaccharides. Glycocodendrimers with 4 or 8 sugar residues were obtained by the reaction of the cyclic carbamates with PAMAM generation 0 and 1 in aqueous media. Glycolipid mimetics containing aliphatic chain in the aglycon were obtained by reaction with corresponding aliphatic amines in pyridine. Glycolipid mimetics containing cholesterol residue were synthesized from a corresponding cholesteryl derivative carrying an amino group in a terminal position of a short linker. Derivatives with diazirine-containing photoactivable aglycons were synthesized by the reaction with ‘photo-benzylamine’ building block containing diazirine group. Cyclic carbamates of sugars can also be used for attachment of sugar residues to proteins in aqueous media, and for the modification of living cells.
Whitehead et al., Cell Chem. Biol. 2017, 24, 1–11
