The synthesis of branched-chain 3'-C-cyanomethyl-2',3'-dideoxy sugar nucleosides of adenine as potential inhibitors of the human immunodeficiency virus.
Condensation of the 3'-ketonucleoside 4 with diethyl cyanomethylphosphonate by a Wittig reaction afforded, after reduction of the unsaturated branched chain sugar nucleoside 5 with sodium borohydride, a mixture of 9-(2',5'-di-O-t-butyldimethylsilyl-3'-C-cyanomethyl-3'-deoxy-beta-D-ribo - and xylofuranosyl) adenines 6 and 7, which were separated after selective removal of the 5'-O-tBDMS group. Acetylation gave the monoacetylated ribo- and the triacetylated xylo compounds 10 and 11. Desilylation using tetrabutylammonium fluoride afforded the partially protected ribo isomer 12. The same treatment of 11 was accompanied by a N----O transacetylation giving the fully protected xylo compound 13a, from which the 2'-O-acetyl group was selectively removed using hydroxylaminium acetate. Treatment of 12 and 13b with phenoxythiocarbonyl chloride followed by deoxygenation with tributyltin hydride in the presence of azobisisobutyronitrile, and deacetylation in methanol saturated with ammonia afforded 9-(3'-C-cyanomethyl-2',3'-dideoxy-beta-D-erythro-pentofuranosyl) adenine 2 and 9-(3'-C-cyanomethyl-2'3'-dideoxy-beta-D-threo-pentofuranosyl) adenine 3.
Halmos
T
T
Institut de Recherches Scientifiques sur le Cancer du CNRS, Villejuif, France.
Montserret
R
R
Antonakis
K
K
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis*; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009904:Optical Rotation; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D007202:Indicators and Reagents; D000225:Adenine