Rhodium-catalyzed iminoiodane-mediated oxyamidation studies of 5-vinyluracil derivatives using aryl and alkyl sulfamates

Abstract

The dirhodium tetraacetate-catalyzed iminoiodane-mediated reaction of 1,3-dimethyl-5-vinyluracil with phenyl sulfamate provided a high yield of 5-(1-acetyl-2-phenylsulfamoyl)ethyluracil via regioselective nucleophilic ring opening by acetate anion of the transiently formed 5-(1,2)-N-phenylsulfonylaziridine intermediate. This 1,2-oxyamidation reaction was found to be general for a variety of aryl- and alkylsulfamates as well as for various 1,3-dialkyl-5-vinyluracil derivatives. Addition of an alcohol to the reaction mixture allowed formation of the corresponding 1-alkoxy products. A selection of the substituted uracil derivatives prepared by this procedure was evaluated for cytotoxic activities in HCT-116 and HepG2 cancer cell lines and showed either no or modest activities. Further evaluation for α-glucosidase inhibition revealed that compounds 15ca and 15da were more active than acarbose, the reference inhibitor. This methodology thus allows efficient preparation of highly functionalized uracil derivatives thereby providing a synthetic route to novel compounds with potentially useful biological activities.