Direct C-glycosylation of guanine analogues: the synthesis and antiviral activity of certain 7- 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-beta-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one) and 8-beta-D-ribofuranosyl-7-deazaguanine (16), respectively. This electrophilic C-glycosylation 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-beta-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.
Girgis
N S
NS
ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
Michael
M A
MA
Smee
D F
DF
Alaghamandan
H A
HA
Robins
R K
RK
Cottam
H B
HB
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006031:Glycosylation; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice; D012672:Semliki forest virus; D014036:Togaviridae Infections / Q000188:drug therapy
D000998:Antiviral Agents; D006151:Guanosine