Synthesis and antimicrobial activity evaluation of novel phosphorylated derivatives of Zidovudine
By S. Subba Reddy, V. Koteswara Rao, K. Venkataramana, C. Suresh Reddy, S. K. Ghosh and C. Naga Raju
A series of novel phosphorylated derivatives of zidovudine (5-15) were synthesized in two step process with high yields. In the first step zidovudine (1) was reacted with bis(2-chloroethyl) phosphoramidicdichloride/4-nitrophenylphosphorodichloridate/4-chloro phenyl phosphorodi-chloridate in presence of triethylamine (TEA) in dry tetrahydrofuran (THF) to yield the intermediates(2-4). They were further reacted with various compounds like monopotassium dihydrogenphosphate and amino acid esters to obtain the title compounds 5-15. The title compounds showed promising antimicrobial activity and it was greatly influenced by the presence of different bio-active groups at phosphorus.
Key words: Phosphorylated derivatives of zidovudine, gram positive bacteria, gram negative bacteria, antimicrobial activity, phosphoramidate monoesters