X-ray, FT-IR, NMR and PM5 structural studies and antibacterial activity of unexpectedly stable salinomycin-benzotriazole intermediate ester

The unexpectedly stable benzotriazole ester of salinomycin (SAL-HOBt) - an intermediate product of the amidation reaction of salinomycin has been isolated and structurally characterised (using a single crystal) by X-ray, FT-IR. NMR and semiempirical methods. The results of the X-ray and spectroscopic studies demonstrated that this intermediate ester exist in the solid state and in solution exclusively as the stable O-acyl form. The molecular structure of SAL-HOBt is stabilised by relatively weak intramolecular hydrogen bonds. The PM5 calculation of possible structures of SAL-HOBt has shown that the O-acyl form is more energetically favourable than its N-oxide-N-acyl isomers. The antimicrobial tests show that SAL-HOBt is active against Gram-positive bacteria and clinical isolates methicillin-resistant Staphylococcus aureus (MIC = 1-2 mu g/ml). (C) 2012 Elsevier B.V. All rights reserved.