title: Synthesis and Potent Anti-HCMV Activity of 2',5',5'-trifluoro-3'-hydroxy-apiosyl Nucleoside Phosphonic Acid Analogues.
abstract: As antiviral nucleosides containing a fluorine atom at 2'-position are endowed with increased stabilization of glycosyl bond, it was of interest to investigate the influence of three fluorine atoms at 2'- and 5'-positions of apiosyl nucleoside phosphonate analogues. Various pyrimidine and purine 2',5',5'-trifluoro-3'-hydroxy-apiose nucleoside phosphonic acid analogues were synthesized from 1,3-dihydroxyacetone. Electrophilic fluorination of lactone was performed using N-fluorodibenzenesulfonimide. Difluorophosphonation was performed by direct displacement of triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding (α,α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield nucleoside phosphonate analogues. Deprotection of diethyl phosphonates provided the final phosphonic acid sodium salts. The synthesized nucleoside analogues were subjected to antiviral screening against various viruses.
authors.affiliation: a BK-21 Project Team, College of Pharmacy, Chosun University , Kwangju , Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: a BK-21 Project Team, College of Pharmacy, Chosun University , Kwangju , Republic of Korea.
authors.forename: Joon Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects*; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D010757:Phosphorous Acids; C570063:phosphonic acid
keywords: 2′,5′,5′-trifluoro-3′-hydroxy-apiose nucleoside phosphonic acid analogues; Antiviral agents; Vorbrüggen reaction