Synthesis and biological properties of the four optical isomers of 5-o-carboranyl-2',3'-didehydro-2',3'-dideoxyuridine.
The four isomers of the 5-o-carboranyl-2',3'-didehydro-2',3'-dideoxyuridine (d4CU) were synthesized and their antiviral activity and cytotoxicity in normal and cancer human cells determined. Coupling of silylated 5-o-carboranyluracil with the protected D/L 2,3-dideoxy-2-phenylselenenylribosylacetates provided after oxidative elimination and deprotection, the desired compounds. The presence of the electron deficient 5-o-carboranyl moiety on uracil influenced the yield of the various isomers. In general, the compounds demonstrated weak anti-human immunodeficiency virus activity in primary human lymphocytes. No marked difference in the biological profile was noted for the various optical isomers, suggesting that the high lipophilicity of these nucleosides imparted by the carboranyl moiety overrides stereochemical considerations in the 2',3'-didehydro-2',3'-dideoxyaglycon moiety.
Atlanta Veterans Affairs Medical Center, Decatur, Georgia 30033, USA.
J C
JC
Graciet
J
J
Shi
R F
RF
Schinazi
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured; D014709:Vero Cells
C114206:5-o-carboranyl-2',3'-didehydro-2',3'-dideoxyuridine; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D015224:Dideoxynucleosides