Microwave-assisted synthesis of novel sulfonamide-based compounds bearing α-aminophosphonate and their antimicrobial properties

Abstract

A series of α-aminophosphonates (3a-3m) bearing the sulfisoxazole moiety was synthesized through one-pot Kabachnik-Fields reaction of sulfisoxazole, diethyl phosphite (DEP) and substituted aldehydes using bismuth (III) triflate [Bi(OTf)3] as a catalyst under microwave reaction conditions. The novel compounds are identified by their spectroscopic data and confirmed by X-ray diffraction studies of diethyl (4-chlorophenyl)(4-(N-(3,4-dimethylisoxazol-5-yl)sulfamoyl)phenylamino) methylphosphonate 3g. The antimicrobial properties of the synthesised agents were examined against a range of bacterial species and C. albicans yeast. Some of the synthesised agents, 3j, 3l and 3m, exhibit potent antimicrobial activities against the five pathogenic microorganisms used in the investigation. Compound 3m is the most promising agents among all the synthesized derivatives, showing a potent and broad-spectrum antibacterial activity. The MIC values are 94.2 and 205.7 µM for 3m and sulfisoxazole, respectively for S. typhi (about 2.1 times potency). The MIC values are 102.8 and 187.0 µM for 3m and sulfisoxazole, respectively for L. monocytogenes. The observed biological properties are explained and supported by QSAR models.