Hexose-modified anti-viral analogues of uridine 5′-disphosphate glucose derivatives

Abstract A series of analogues of the anti-viral 5′- O -[[[[(tetrabenzyl-, or tetrabenzoyl-α- d -glucopyranosyl)oxy]-carbonyl]amino]sulfonyl]uridine, in which the α-glucose moiety has been replaced by α-mannose, or galactose, 2-acetamido-2-deoxy-α-glucopyranose, 2-deoxy-α-, and β-glucopyranose, 6-deoxy-α-, and β-glucopyranose and 2,4-dideoxy-α-glucopyranose, has been synthesized by reaction of the corresponding protected hexose having the 1-OH free with chlorosulfonyl isocyanate and 2′,3′- O -isopropylideneuridine. 5′- O -[[[[(2″,3″,4″,6″-Tetra- O -benzoyl-α- d -mannopyranosyl)oxy]carbonyl]- amino]sulfonyl]-2′,3′- O -isopropylideneuridine( 13 ), 5′- O -[[[[(2″,3″,4″,6″-tetra- O -benzoyl- and 2″,3″,4″,6″-tetra- O -benzyl-α- d -galactopyranosyl)oxy]carbonyl]amino]sulfonyl]-2′,3′- O -isopropylideneuridine ( 18 and 19 ), 5′- O -[[[[(2″-acetamido-2″-deoxy-3″,4″,6″-tri- O -benzoyl- and 3″,4″,6″-tri- O -benzoyl-2″-deoxy-α- d -glucopyranosyl)oxy]carbonyl]amino]sulfonyl]-2′,-3′- O -isopropylideneuridine ( 20 and 21 ) and the deisopropylidenated derivatives of 13 and 21 , showed anti-viral activity similar to that of the corresponding glucose analogues as determined by the inhibition of the cytopathic effect induced by HSV-1 replication.