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

ABSTRACT: 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.

SUBMITTER: Sonousi A

PROVIDER: S-EPMC6595968 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Sonousi Amr A Shcherbakov Dimitri D Vasella Andrea A Böttger Erik C EC Crich David D

MedChemComm 20190425 6

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'-de ...[more]

PMID: 31303992

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