Generation of molecular diversity on N-acetyllactosamine via O-cyanomethyl ethers

The ability to generate molecular diversity around a natural carbohydrate ligand taking advantage of the rich chemistry of the nitrile functional group was demonstrated by synthesizing 24 derivatives of N-acetyllactosamine (LacNAc). The disaccharides prepared carried carboxymethyl, amidinomethyl, aminoethyl, and carbamoylmethyl substituents projecting from each of the six OH groups. The resulting LacNAc derivatives present new structural features with either negatively charged, positively charged, or polar-neutral small substituents sampling the entire periphery of the molecule. These new derivatives should be useful probes for studying carbohydrate-protein interactions in general, and for designing inhibitors of N-acetyllactosamine-binding proteins in particular.