Design, synthesis and cytotoxicity of a new series of isoxazolidine based nucleoside analogues

5‐Arylisoxazolidin‐3‐yl‐3‐diethoxyphosphonates have been synthesized from N‐methyl‐C‐diethoxyphosphorylnitrone and vinyl aryls in good yields and their transformation into the respective phosphonic acids has been accomplished via dealkylation procedure using trimethylsilyl bromide. Phosphonates having 1‐ and 2‐naphthyl substituents at C5 in the isoxazolidine ring as well as the respective phosphonic acids have been found cytotoxic to HeLa and K562 cells with IC₅₀ in the 0.1–0.3 mM range. Preliminary studies on mechanism of action imply that intercalation to DNA is not responsible for their cytotoxic properties.