Direct C-glycosylation of guanine analogues: the synthesis and antiviral activity of certain 7- and 9-deazaguanine C-nucleosides.

Abstract

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.

• Authors: N S Girgis, M A Michael, D F Smee, H A Alaghamandan, R K Robins, H B Cottam
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 33 Issue 10 Pg. 2750-5 (Oct 1990) ISSN: 0022-2623 [Print] United States
• PMID: 2170645 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Guanosine

Topics

• Animals
• Antiviral Agents (chemical synthesis, chemistry, therapeutic use)
• Chemical Phenomena
• Chemistry, Physical
• Glycosylation
• Guanosine (analogs & derivatives, chemistry)
• Mice
• Semliki forest virus
• Togaviridae Infections (drug therapy)