ИСТИНА

Acyclic nucleoside and nucleotide phosphonate analogues are mainly applicable as broad spectrum antivirals and offer a great scope for research. We have synthesized new nucleotide analogues with oxime fragment in the chain: 9-{2-[(Phosphonomethyl)oximino]ethyl}adenine, -guanine and 9-{2-[(phosphonomethyl)oximino]propyl}adenine. The syntheses have been achieved by the condensation of two intermediates at final steps: diethyl aminooxymethylphosphonate with the corresponding aldehydes or ketones. New findings for Mitsunobu reaction and isolation procedures allowed to afford higher conversions for the products. An effective method of detection of aminooxymethylphosphonates and oximes was developed. In addition, we evaluated different bases for the reaction with nucleobases in order to improve N9-isomer yield. Unexpectedly, cleaving esters at the final step of phosphonates resulted back to an inseparable mixture of syn/anti-oxime anionic products. Similar synthesis was applied for the guanine analogue and the ketoxime analogue was obtained additionally. Compounds have been investigated and demonstrated moderate activity on viruses, such as HIV, HSV, HCMV and HCV replicon system, and showed low toxicity.