Based on the principle of molecular hybridization, fifteen sulfonamide derivatives containing amino acid moiety were designed and synthesized to evaluate their antibacterial activities. First, benzenesulfonyl amino acid(intermediate I) was synthesized by the reaction of benzenesulfonyl chloride with amino acids. Then, α-aminophosphonate (intermediate II) was prepared from aromatic aldehyde, phosphite, ammonium acetate and Al(OTf)3 in one pot method. Finally, intermediate I and II were condensed to obtain the target products, and their structures were confirmed by 1H-NMR, 13C-NMR and MS. The results showed that these compounds had the most significant activities against E. coli and FREC. Among them, the MIC of Ⅲb, Ⅲc, Ⅲh and Ⅲm to E. coli was 16 μg/mL, and the MIC of Ⅲn against E. coli was 8 μg/mL, which was not lower than that of the control drug Oxacillin. The MIC of Ⅲb, Ⅲh, Ⅲm and Ⅲn against FREC were 32, 32, 32 and 16 μg/mL, respectively, which were superior to the control drugs Oxacillin and Norfloxacin.