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

GRAPHICAL ABSTRACT

Abstract

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.

Keywords:

• 6-Chloropurine
• Phosphonamidate derivatives
• antimicrobial activity
• Antioxidant activity