Document 0243
 DOCN  M9650243
 TI    Stereoselective synthesis, chemistry and antiviral evaluation of
       1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)thym- ine
       derivatives.
 DT    9605
 AU    Wengel J; Schinazi RF; Caruthers MH; Department of Chemistry and
       Biochemistry, University of Colorado,; Boulder 80309-0215, USA.
 SO    Bioorg Med Chem. 1995 Sep;3(9):1223-9. Unique Identifier : AIDSLINE
       MED/96103865
 AB    A series of novel 3'-C-branched 2',3'-dideoxynucleosides have been
       synthesized and evaluated as anti-HIV agents. Hydroboration of
       2',3'-dideoxy-3'-C-methylene nucleoside proceeded regio- and
       stereoselectively to give 1-(2,3-dideoxy-3-C-hydroxy
       methyl-5-O-trityl-beta-D-threo-pentofuranosyl)thymine (5) after
       oxidation. 3'-C-Chloromethyl and 3'-C-iodomethyl 5'-O-protected
       2',3'-dideoxynucleosides 9 and 12 were obtained from 5 by reaction with
       carbon tetrachloride/triphenylphosphine and methyltriphenoxyphosphonium
       iodide, respectively. Arbuzov reaction of 12 with triethyl phosphite
       afforded 3'-C-(diethyl-phosphono)methyl 5'-O-protected
       2',3'-dideoxynucleoside 14. Compounds 5, 9, 12 and 14 were detritylated
       to give
       1-(3-C-chloromethyl-2,3-dideoxy-beta-D-threo-pentofuranosyl)thymi- ne
       (10), 1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo-pentofuranosyl)-thy-
       mine (11),
       1-(2,3-dideoxy-3-C-iodomethyl-beta-D-threo-pentofuranosyl)thymine (13)
       and 1-(2,3-dideoxy-3-C-(O,O'-diethylphosphono)methyl-beta-D-threo-
       pentofuranosyl)thymine (15), respectively. These nucleoside analogues
       were evaluated for antiviral activity against human immunodeficiency
       virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro.
       Compound 5 demonstrated selective antiviral activity against HIV-1 but
       not HSV-1.
 DE    Antiviral Agents/CHEMISTRY/*CHEMICAL SYNTHESIS/*PHARMACOLOGY  Cells,
       Cultured  Herpesvirus 1, Human/DRUG EFFECTS  Human  HIV-1/DRUG EFFECTS
       Leukocytes, Mononuclear/VIROLOGY  Microbial Sensitivity Tests
       Stereoisomers  Support, Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.
       Support, U.S. Gov't, P.H.S.  Thymine/*ANALOGS &
       DERIVATIVES/CHEMISTRY/CHEMICAL SYNTHESIS/  PHARMACOLOGY  Trityl
       Compounds/CHEMISTRY/CHEMICAL SYNTHESIS/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).