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


Sonousi, Amr; Shcherbakov, Dimitri; Vasella, Andrea; Böttger, Erik C; Crich, David (2019). Synthesis, ribosomal selectivity, and antibacterial activity of netilmicin 4'-derivatives. MedChemComm, 10(6):946-950.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Molecular Medicine
Life Sciences > Pharmacology
Life Sciences > Pharmaceutical Science
Life Sciences > Drug Discovery
Physical Sciences > Organic Chemistry
Language:English
Date:1 June 2019
Deposited On:07 Jan 2020 11:00
Last Modified:29 Jul 2020 12:08
Publisher:Royal Society of Chemistry
ISSN:2040-2503
OA Status:Closed
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/c9md00153k
PubMed ID:31303992

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