ORGN 657 |
| 3-Deaza-adenosine analogs display broad-spectrum antiviral activity. Introduction of one or more fluorine atoms to biologically active compounds can increase its bioavailability, liphopilicity and bioactivity. Introduction of C-F bond at 3-position of purine could mimic not only regular adenine and guanine bases but also 3-deaza adenine and 3-deaza guanine bases. Although 3-fluoro-3-deaza adenosine synthesis has been reported, hurdles in applying this reported methodology to modified sugar analogs of 3F-3-deaza-Ad demands general and efficient methodology. Highly inert SNAr reactivity of chloroimidazoprydine nucleosides towards nucleophiles such as ammonia is a main drawback in the synthesis of 3-deaza-Ad. During the course of investigations of SNAr reactions of 6-chloro-3-fluoro-imidazopyridine nucleosides, we found that SNAr reaction of 3-fluorine group is more facile than 6-chlorine with sulphur nucleophiles such as sodium thiomethoxide. This observation led us to investigate SNAr reactivity of 3,6-difluoro-imidazopyridine nucleosides with ammonia nucleophiles towards the development of general and efficient methodology for the synthesis of 3-fluoro-3-deaza-Ad nucleosides. As a result of this investigation, we wish to present efficient and general synthesis of 3-fluoro-3-deaza-adenosine analogs.
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Proteins, Peptides, and Nucleotides
8:00 AM-11:00 AM, Wednesday, 16 March 2005 Convention Center -- Room 9, Oral
Division of Organic Chemistry |
