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

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Abstract
A series of analogs of UDP-glucose and UDP-glucosamine was 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-.alpha.-D-glucopyranose and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-.alpha.-D-glucopyranose with chlorosulfonyl isocyanate and 2,3''-O-isopropylideneuridine. Isopropylidene and acetyl groups of the resulting 5''-O-[[[[(.alpha.-D-glucopyranosyl)oxyl]carbonyl]amino]sulfonyl]-2'',3''-O-isopropylideneuridine derivatives were removed by reaction with a TFA [trifluoroacetic acid]/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-.alpha.-D-glucopyranosyl)oxyl]carbonyl]amino]sulfonyl]-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 [Herpes Simplex Virus type 1] replication and by the plaque assay method. Compound 13 inhibited glycosylation of proteins in HSV-1 infected HeLa cells.