Synthesis, ribosomal selectivity, and antibacterial activity of netilmicin 4'-derivatives

Sonousi, A., D. Shcherbakov, A. Vasella, E. C. Böttger, and D. Crich, "Synthesis, ribosomal selectivity, and antibacterial activity of netilmicin 4'-derivatives", MedChemComm, vol. 10, issue 6: Royal Society of Chemistry, pp. 946 - 950, 2019/04/25.


Halogenation of a suitably protected netilmicin derivative enables preparation of 4'-chloro-, bromo-, and iodo derivatives of netilmicin after deprotection. Suzuki coupling of a protected 4'-bromo derivative with phenylboronic acid or butyltrifluoroborate affords the corresponding 4'-phenyl and 4'-butyl derivatives of netilmicin. Sulfenylation of suitably protected netilmicin derivative with ethanesulfenyl chloride followed by deprotection affords 4'-ethylsulfanylnetilmicin. All netilmicin 4'-derivatives displayed reduced levels of inhibition for prokaryotic ribosomes and reduced antibacterial activity against typical Gram-positive and Gram-negative strains. None of the derivatives displayed enhanced target selectivity.



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