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 μg/ml).

► Salinomycin–benzotriazole intermediate ester has been synthesised and characterised.
► X-ray, FT-IR, NMR and PM5 studies showed that ester exist in O–acyl form.
► The conversion of O–acyl form to N–oxide–N–acyl form is not observed.