Synthesis of pyrazolo-azepinone derivatives via Morita-Baylis-Hillman chemistry as potent antimicrobial agents

A new approach has been devised toward an efficient synthesis of pyrazolo[3,4-c]azepinone derivatives using the Morita-Baylis-Hillman (MBH) reaction of ethyl 4-formyl-pyrazole-3-carboxylates. The MBH adducts were acetylated and exposed to S(N)2 ' reaction with various amines to afford the diversely substituted pyrazolo[3,4-c]azepinones. It was observed that the feasibility of intramolecular condensation was controlled by the stereochemistry across the double bond and the bulkiness of the ester functionality. The antimicrobial evaluation of all the synthetic derivatives was carried out using broth microdilution susceptibility tests against various Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungal strains (Candida albicans and Aspergillus niger). The compounds 13aBY (MIC 0.39 mu g mL(-1)), 13aDX (MIC 0.19 mu g mL(-1)) and 13dBX (MIC 0.19 mu g mL(-1)) were found to be the most active in the series.