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Synthesis of neamine-derived pseudodisaccharides by stereo- and regio-selective functional group transformations.
- Source :
-
Organic & biomolecular chemistry [Org Biomol Chem] 2009 Oct 21; Vol. 7 (20), pp. 4252-66. Date of Electronic Publication: 2009 Aug 12. - Publication Year :
- 2009
-
Abstract
- Neamine is normally found as a core structure of aminoglycoside antibiotics. In order to understand the relationship between the antibiotic activity and the configurations of the functional groups of neamine, a series of novel neamine analogues with functional group manipulations on the 2-deoxystreptamine (2-DOS) ring or the sugar ring were designed and synthesized. The synthetic approach involved the construction of 2-DOS derivatives by catalytic Ferrier II rearrangement, stereo- and regio-selective functional group transformations, glycosyl coupling reaction, and global deprotection. Of the synthetic neamine analogues, four compounds showed comparable 16S rRNA binding affinities with neamine, whereas they displayed lower binding affinities towards 18S rRNA than neamine, implying a lower toxicity to mammals. This strategy might have applications in the chemical synthesis of other neamine derivatives and new aminoglycoside antibiotics with improved biological activities.
- Subjects :
- Anti-Bacterial Agents chemical synthesis
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents metabolism
Anti-Bacterial Agents pharmacology
Biomimetics
Disaccharides chemical synthesis
Disaccharides metabolism
Disaccharides pharmacology
Glycosylation
Hexosamines biosynthesis
Hexosamines chemical synthesis
Hexosamines chemistry
Pseudomonas aeruginosa drug effects
RNA metabolism
Stereoisomerism
Substrate Specificity
Disaccharides chemistry
Framycetin chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1477-0539
- Volume :
- 7
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Organic & biomolecular chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19795065
- Full Text :
- https://doi.org/10.1039/b907518f