title: 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.
authors.affiliation: a BK-21 Project Team, College of Pharmacy , Chosun University , Kwangju , Republic of Korea.
authors.forename: Eunae
authors.initials: E
authors.lastname: Kim
authors.forename: Seyeon
authors.initials: S
authors.lastname: Kim
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D000085:Acetates / Q000737:chemistry; D000225:Adenine / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001577:Benzophenones / Q000737:chemistry; D002855:Chromatography, Thin Layer; D015195:Drug Design; D005985:Glyceraldehyde / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D009705:Nucleosides / Q000737:chemistry*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000737:chemistry; D013053:Spectrophotometry; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D000085:Acetates; D019380:Anti-HIV Agents; D001577:Benzophenones; C572123:N-fluorodibenzenesulfonimide; D009705:Nucleosides; D010757:Phosphorous Acids; D013449:Sulfonamides; C570063:phosphonic acid; D005985:Glyceraldehyde; D006147:Guanine; D006859:Hydrogen; D000225:Adenine; D010746:Phosphonoacetic Acid
keywords: 2′,3′-difluorinated nucleoside; Antiviral agent; deoxythreosyl nucleoside; phosphonic acid nucleoside