New N-Linked Phosphonamidate Derivatives of 6-Chloropurine: Synthesis and Evaluation of Antimicrobial and Antioxidant Activities

A series of new phosphonamidate derivatives 10a-j of 6-chloropurine was prepared for biological interest in one-pot three-step synthesis. The monochloride key intermediate, 4-chlorophenyl-6-chloro-9H-purin-9-yl-phosphonochloridate (8) was prepared by the reaction of 4-chlorophenyl phosphorodichloridate (7) with sodium 6-chloropurin-9-ide (6), which was obtained from 6-chloropurine (5) in the presence of sodium hydride. Finally, the intermediate 8 was allowed to react with various amines 9a-j to give the 4-chlorophenyl-6-chloro-9H-purin-9-yl (substituted amino) phosphonamidates 10a-j. All the new compounds synthesized were screened for their in vitro antimicrobial and antioxidant activities. Compounds 10c, e-g showed potent inhibition activity on the growth of bacterial strains, compounds 10c, h-j displayed a similar inhibition activity on fungal strains, while compounds 10e-i showed promising antioxidant activity.