Efficient sialyltransferase inhibitors based on glycosides of N-acetylglucosamine.

D-Glucosamine was transformed into phenyl and 2-benzoyloxyethyl N-acetylglucosamine beta-glycosides 6a and 6b, respectively. Transformation of 6a,b into 6-O-unprotected N-acetylglucosamine derivatives 9a,b permitted the generation of an aldehyde group in the 6-position. Treatment of these intermediates with base afforded unsaturated aldehyde derivatives 10a,b, which are structural mimics of 2,3-dehydroneuraminic acid. H-Phosphonate addition to the aldehyde group and attachment of the cytidine monophosphate residue to the generated hydroxy group gave fully protected transition state analogues of cytidine monophosphate-N-acetylneuraminic acid 14a,b. Liberation of the unprotected compounds 1ah,l and 1bh,l led to excellent inhibitors of alpha(2-6)-sialyltransferase from rat liver. Variation of the protective group cleavage procedure for 14a,b led to formal loss of phosphate, thus resulting in diene derivatives (E)-/(Z)-2a,b, which also exhibited inhibitory properties.