Synthesis and Antiviral Activity of 5′‐ O ‐(Substituted) Sulfamoyl Pyrimidine Nucleosides

5′‐ O ‐[ N ‐(Aminoacyl or isobutyryl)sulfamoyl]uridines 4a‐e, 5a‐e and 5′‐ O ‐[ N ‐(isopropyl)sulfamoyl]cytidines 7 – 9 have been synthesized and tested against herpes simplex virus type 2. Condensation of 2′,3′‐ O ‐isopropylidene‐5′‐ O ‐sulfamoyluridine with the N ‐hydroxysuccinimide esters of Boc‐Gly, Boc‐ L ‐Ala, Boc‐ D ‐Ala and Boc‐ L ‐Phe, gave 4a‐d which, on deprotection under acidic conditions, provided 5a‐d . A similar condensation of 2′,3′‐di‐ O ‐acetyl‐5′‐ O ‐sulfamoyluridine with the N ‐hydroxysuccinimide ester of isobutyric acid afforded 4e which on deacylation led to 5e . 5′‐ O ‐[ N ‐(Isopropyl)sulfamoyl]‐2′,3′‐ O ‐isopropylidenecytidine ( 7 ) was prepared by reaction of 2,3′‐ O ‐isopropylidene‐4‐ N ‐[(dimethylamino)methylene] cytidine with N ‐isopropylsulfamoyl chloride. Acidic hydrolysis of 7 provided 8 which, upon acetylation, gave the corresponding 2′,3′‐di‐ O ‐acetyl derivative 9 . Compounds 7 – 9 show antiviral effect. Structure‐activity relationships are discussed.