Synthesis of Novel 3-spirocephalosporins and Evaluation of their Antibacterial Activity.

BACKGROUND AND

OBJECTIVES

Despite the well-known antibacterial activity of cephalosporins, their analogous spirocyclic derivatives have not been adequately evaluated. Thus, this work aimed to prepare a series of novel 3-spirocephalosporins and evaluate their antibacterial activity.

MATERIALS AND

METHODS

Novel 3-spirocephalosporins were prepared through a one-pot thioalkylation of chloromethyl cephalosporin GCLE with a range of 1,2,4-triazolidine-3- thiones, followed by intramolecular Michael addition to the generated dihydrothiazine ring. The reaction was performed at room temperature under basic conditions (K2CO3, acetone, H2O). The antibacterial activities of the synthesized compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria.

RESULTS

Most targets were obtained in moderate yield, and their structures were confirmed by 1H and 13C NMR spectral techniques. All the tested compounds exhibited antibacterial activity against methicillin-resistant S. aureus.

CONCLUSION

Seven novel thiazolidine-bearing 3-spirocephalosporins were prepared, and most of them were potent against Gram-positive bacteria. Likely, the replacement of 1,2,4- triazolidine-3-thiones with other heterocycles containing bidentate nucleophiles in advantageous positions could lead to different biologically active spirocephalosporins.