DIRECT C-GLYCOSYLATION OF GUANINE ANALOGS - THE SYNTHESIS AND ANTIVIRAL ACTIVITY OF CERTAIN 7-DEAZAGUANINE AND 9-DEAZAGUANINE C-NUCLEOSIDES

C-Glycosylation of two guanine analogues, 9-deaza- and 7-deazaguanine, has been achieved under Friedel-Crafts conditions, providing a direct synthetic route to 9-deazaguanosine (4; 2-amino-7-β-D-ribofuranosyl-5H-pyrrolo-[3,2-d]pyrimidin-4(3H)-one) and 8-β-D-ribofuranosyl-7-deazaguanine (16), respectively. This electrophilic Cglycosylation was applied successfully to six guanine and substituted-guanine analogues resulting in yields of approximately 50%. This represents the first reported C-ribosylation of preformed nitrogen heterocycles isosteric with guanine. These C-nucleosides were evaluated for their ability to provide protection against a lethal Semliki Forest virus infection in mice, relative to 7-thia-8-oxoguanosine which was used as a positive control. Two of the C-nucleosides, 2-amino-6-chloro-5-methyl-7-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (12) and the corresponding 6-bromo derivative (13), showed good prophylactic activity in this virus model system. © 1990, American Chemical Society. All rights reserved.