Synthesis of Gentamicins C1, C2, and C2a and Antiribosomal and Antibacterial Activity of Gentamicins B1, C1, C1a, C2, C2a, C2b, and X2
Abstract
Complementing our earlier syntheses of the gentamicins B1, C1a, C2b, and X2, we describe the synthesis of gentamicins C1, C2, and C2a characterized by methyl substitution at the 6′-position, and so present an alternative access to previous chromatographic methods for accessing these sought-after compounds. We describe the antiribosomal activity of our full set of synthetic gentamicin congeners against bacterial ribosomes and hybrid ribosomes carrying the decoding A site of the human mitochondrial, A1555G mutant mitochondrial, and cytoplasmic ribosomes and establish structure–activity relationships with the substitution pattern around ring I to antiribosomal activity, antibacterial resistance due to the presence of aminoglycoside acetyl transferases acting on the 6′-position in ring I, and literature cochlear toxicity data. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000625348Publication status
publishedExternal links
Journal / series
ACS Infectious DiseasesVolume
Pages / Article No.
Publisher
American Chemical SocietySubject
gentamicins; mitochondrial and cytoplasmic ribosomes; antibacterial resistance; ototoxicityMore
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