Synthesis and Bioactivity of Novel Phosphonate Derivatives Containing Thiophene and Sulfonamide Group / 中国药学杂志

ABSTRACT

OBJECTIVE: To design and synthsize a series of novel phosphonate derivatives. METHODS: First, the intermediates of aminophosphonate was prepared by solvent-free one-pot method using aromatic aldehyde, ammonium acetate, diethyl phosphite and Al(OTf)3 as raw materials. Then, using basic ionic liquid OH as catalyst, the target compounds were synthesized by the reaction of intermediate with sulfonyl chloride. And the antibacterial activities of the products were evaluated by the agar dilution method. RESULTS: Twelve title compounds were synthesized, and their structures were clearly established by 1H-NMR, 13C-NMR and MS. The results showed that the derivatives have different inhibitory activities against Gram-positive bacteria and Gram-negative bacteria, especially the compounds Ⅱe and Ⅱk showed better activity, the MIC of the former for S.aureus, E. coli, MRSA and MREC was 32, 64, 32, and 128 μg•mL-1, respectively, and the MIC of the latter was 16, 64, 32, and 64 μg•mL-1, respectively. Its antibacterial activities were significantly better than that of the control drug sulfadiazine, and close to that of gatifloxacin. CONCLUSION: These derivatives have potential antibacterial activity, which is worth for further structural optimization and study.