Uridine 5'-diphosphate glucose analogues. Inhibitors of protein glycosylation that show antiviral activity

Article abstract of DOI:10.1021/jm00379a010

A series of analogues of uridine 5'-diphosphate glucose and uridine 5'-diphosphate glucosamine have been synthesized by reaction of 2,3,4,6-tetra-O-benzyl-, 2,3,4,6-tetra-O-benzoyl-, 2,3,4,6-tetra-O-acetyl-, and 2,3,4,6-tetra-O-palmitoyl-α-D-glucopyranose and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranose with chlorosulfonyl isocyanate and 2',3'-O-isopropylideneuridine. Isopropylidene and acetyl groups of the resulting 5'-O-[[[[(α-D-glucopyranosyl)oxy]carbonyl]amino]sulfonyl]-2',3'-O-isoprop ylideneuridine derivatives were removed by reaction with a TFA/water (5:1) mixture and methanolic ammonia, respectively. The 5'-O-[[[[(2'',3'',4'',6''-tetra-O-benzyl- and 2'',3'',4'',6''-tetra-O-benzoyl-α-D-glucopyranosyl)oxy]carbonyl]amino]sul fonyl]-2',3'-O-isopropylideneuridine (13 and 19) and the corresponding deisopropylidenated derivatives showed antiviral activity as determined by the inhibition of the cytopathic effect induced by HSV-1 replication and by the plaque assay method. Compound 13 inhibited glycosylation of proteins in HSV-1 infected HeLa cells.