Synthesis of Novel 2′,3′-Difluorinated 5′-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

Abstract

A novel route for the synthesis of 2′,3′-difluorinated 5′-deoxythreosyl phosphonic acid nucleosides from glyceraldehyde using the Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate is described. The second fluorination at the 2′-position was an electrophilic reaction performed using N-fluorodibenzenesulfonimide. Glycosylation reactions between the nucleosidic bases and glycosyl donor 9 generated nucleosides that were further phosphonated and hydrolyzed to produce the desired nucleoside analogues. The synthesized nucleoside analogues 13, 16, 20, and 23 were tested for anti- human immunodeficiency virus (HIV) activity as well as cytotoxicity. Adenine derivative 16 showed significant anti-HIV activity up to 100 μM.

Keywords:

• Antiviral agent
• 2′,3′-difluorinated nucleoside
• deoxythreosyl nucleoside
• phosphonic acid nucleoside