SYNTHESIS AND ANTIVIRAL EVALUATION OF CERTAIN NOVEL PYRAZINOIC ACID C-NUCLEOSIDES

Pyrazine (1,4-diazine) C-nucleosides constitute a rare class of nuclei c acid analogues that has only recently been reported in the literatur e. As part of our ongoing investigation into the synthesis and reactiv ity of these compounds, we have developed an electrophilic esterificat ion of a lithiated pyrazine C-nucleoside (1) to give, following deprot ection, the versatile intermediate ethyl oro-6-(beta-D-ribofuranosyl)p yrazine-2-carboxylate (4). This intermediate was subjected to a variet y of reaction conditions to generate a series of pyrazinoic acid C-nuc leosides. These compounds, along with 3,5-dichloro-2-(beta-D-ribofuran osyl)pyrazine (2) and 4, were evaluated for antiviral activity and cyt otoxicity. No significant activity was observed for compounds 2 and 5- 9, but 4 was active against two herpes viruses and cytotoxic in the mi cromolar range.