title: Synthesis and antiviral evaluation of some beta-L-2', 3'-dideoxy-5-chloropyrimidine nucleosides and pronucleotides.
abstract: The synthesis and in vitro anti human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activities of some unnatural beta-L-nucleoside enantiomers related to the anti-HIV compound 2', 3'-dideoxy-3'-fluoro-5-chlorouridine (beta-D-3'Fdd5ClU) are reported. In contrast to beta-D-3'Fdd5ClU, beta-L-3'Fdd5ClU and the other L-congeners were devoid of significant anti-HIV effects, but beta-L-2',3'-dideoxy-5-chlorocytidine (beta-L-dd5ClC) and beta-L-2', 3'-dideoxy-3'-fluoro-cytidine (beta-L-3'FddC) showed a distinct anti-HBV activity. Three mononucleoside phosphotriester derivatives with S-pivaloyl-2-thioethyl (t-BuSATE) groups as biolabile phosphate protective groups were also synthesized. The bis(t-BuSATE) derivative of beta-D-3'Fdd5ClU retained anti-HIV activity in thymidine kinase deficient (TK(-)) CEM cells.
authors.affiliation: Laboratoire de Chimie Organique Biomoléculaire de Synthèse, UMR CNRS 5625, Case Courrier 008, Université Montpellier II, Place Eugène Bataillon, 34095, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Pierra
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: A
authors.initials: A
authors.lastname: Van Aerschot
authors.forename: P
authors.initials: P
authors.lastname: Herdewijn
authors.forename: A
authors.initials: A
authors.lastname: Faraj
authors.forename: A G
authors.initials: AG
authors.lastname: Loi
authors.forename: J P
authors.initials: JP
authors.lastname: Sommadossi
authors.forename: G
authors.initials: G
authors.lastname: Gosselin
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000998:Antiviral Agents; D015224:Dideoxynucleosides