Synthesis and antiviral evaluation of novel 4'-trifluoromethylated 5'-deoxyapiosyl nucleoside phosphonic acids.
On the basis of the discovery that the threosyl nucleoside phosphonate PMDTA is a potent anti-HIV compound, we synthesized several 4'-trifluoromethyl-5'-deoxyapiosyl nucleoside phosphonic acids and evaluated their anti-HIV activity. An efficient synthetic route was optimized, starting from an α-trifluoromethyl-α,β-unsaturated ester. Glycosylation of the purine nucleosidic bases with a glycosyl donor yielded modified nucleoside intermediates, which were then phosphonated and hydrolyzed to provide the targeted nucleoside analogs. Once synthesized, the anti-HIV and cytotoxic activities of each analog were evaluated. None of the analogs showed significant anti-HIV activity at concentrations up to 100 μM.
a BK-21 Project Team, College of Pharmacy , Chosun University , Kwangju , Republic of Korea.
Seyeon
S
Kim
Eunae
E
Kim
Wonjae
W
Lee
Joon
J
Hee Hong
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000821:virology; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000494:pharmacology*
D019380:Anti-HIV Agents; D009705:Nucleosides; D010757:Phosphorous Acids
4′-trifluoromethylated nucleoside; 5′-deoxyapiosyl nucleoside; Antiviral agent; nucleoside phosphonic acid