Microwave Assisted Synthesis of New Imines of 7-Aminocephalosporinic Acid as Potent Antibacterial Agents
A.B. Thomas, S.P. Moharil, R.K. Nanda, S.G. Dhokrat, L.K. Kothapalli and M.V. Nanwatkar
Affiliation: Department of Pharmaceutical Chemistry, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 18, Maharashtra, India.
Keywords: Alpha-halo ketones, fragment-based design, imines of 7-ACA, microwave irradiation, N-heterocycles.
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.
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