Synthesis and anti-HIV activity of thymidine analogues bearing a 4'-cyanovinyl group and some derivatives thereof.
Treatment of 3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine (4) with potassium or magnesium nitromethanide afforded in good yield the resolvable epimeric mixture of the expected blocked nitronucleosides 5 which upon dehydration led to the corresponding E-nitroenofuranosylthymidine 6. Nucleophilic attack of cyanide onto the nitrovinyl group led to a nucleoside analogue bearing a terminal 1-cyanovinyl group (7), a soft electrophilic group which, upon reaction with benzeneselenol, underwent a conjugate addition to the phenylselenonucleoside derivative 9. All these compounds, eventually de-O-silylated, were subject of in vitro biological testing, some exhibiting interesting cytotoxic or antiviral properties.
Tronchet
J M
JM
Department of Organic Pharmaceutical Chemistry, University of Geneva, Sciences II, Switzerland.
Kovacs
I
I
Dilda
P
P
Seman
M
M
Andrei
G
G
Snoeck
R
R
De Clercq
E
E
Balzarini
J
J
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008826:Microbial Sensitivity Tests; D012821:Silanes / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C458779:3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine; D019380:Anti-HIV Agents; D012821:Silanes; D013936:Thymidine