Synthesis and bioactivity of phosphorylated derivatives of stavudine

Abstract

Novel phosphorylated derivatives of stavudine were synthesized by the reaction of bis(2-chloroethyl)phosphoramidic dichloride/4-nitrophenyl phosphorodichloridate with various cyclic amines and amino acid esters in the presence of triethylamine in dry tetrahydrofuran through the corresponding monochloride intermediates 2a-l. Further reaction of the intermediates 2a-l with stavudine in tetrahydrofuran and pyridine in the presence of triethylamine formed the title compounds 4a-l. Their structures were characterized by IR, ¹H-, ¹³C-, ³¹P-NMR and mass spectral data analyses. They exhibited good antibacterial and antioxidant activities. Their bioactivity was greatly influenced by the different groups present at the phosphorus.