A series of new imines of 7-Aminocephalosporinic acid (7-ACA) were synthesized by fragment-based design using smaller and functionally simpler adducts like alpha-halo ketones, N-heterocycles and 7-ACA with good success to generate chemical compounds with drug-like properties effective against Staphylococcus aureus and Pseudomonas aeruginosa which are resistant to several antibiotics and are responsible for a large number of community acquired infections. In the first step, N-aryl substituted ketones were synthesized in excellent yields (90-96%) in a single step reaction (Scheme 1) with various heterocyclic rings in the presence of solvents like ethanol/DMF using microwave irradiation method in shorter reaction times (10-12 mins) with higher yields (90-95%). Further, the microwave assisted synthesis of imines of 7-ACA from corresponding ketones (Scheme 2) with ethanol as the solvent in the presence of molecular sieves resulted in target compounds with improved yield (90-94%) in short reaction times (12-14 min). The use of microwave assisted synthetic route and greener and environmentally benign solvents resulted in improvement of rates (energy savings), yields and selectivity (reduced wastes) of the target compounds.

Alpha-halo ketones, fragment-based design, imines of 7-ACA, microwave irradiation, N-heterocycles.

Department of Pharmaceutical Chemistry, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 18, Maharashtra, India.