- ANTIBACTERIAL SIDEROMYCINS
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A compound, comprising: an Fe(III)-binding and/or Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; and daptomycin covalently bound to the linker, or, if no linker is present, then to the siderophore; or pharmaceu
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- Method for preparing desferrioxamine B and homologs thereof
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A new and versatile route to N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]hydroxyamino]pentyl]-N-(5-aminopentyl)-N-hydroxybutanediamide, desferrioxamine B (DFO) is described. N-Benzyloxy-1,5-diaminopentane is selectively protected at the
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- A versatile synthesis of deferrioxamine B
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A new and versatile route to N'-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]-hydrox yamino]pentyl]-N-(5-aminopentyl)-N-hydroxybutanediamide, deferrioxamine B (DFO), is described. The key improvement over the two prior routes was replacement of the nitrile in 2 with a tert-butoxycarbonyl-protected amino terminus. Elimination of the nitrile improved the kinetics of hydrogenation in that the benzyl groups of 12 were cleaved more rapidly than saturation of the cyano group of 2, and a potential overreduction byproduct (4) was thus avoided. N-(Benzyloxy)-1,5-diaminopentane (6) was selectively protected at the primary amino site with a tert-butoxycarbonyl (BOC) group, providing 7. This was reacted at the (benzyloxy)amine with succinic anhydride to produce carboxylic acid 8, which was in turn acylated regiospecifically with diamine 6 at the primary amine to give (benzyloxy)amine 9. The previous two steps were reiterated to afford DFO reagent 11. This synthon allows for modification of DFO at either end of the molecule, thus providing more flexibility in accessing DFO analogues than any prior route. Acetylation of 11, followed by hydrogenolysis and tert-butoxycarbonyl group removal, furnished DFO.
- Bergeron,McManis,Phanstiel IV,Vinson
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p. 109 - 114
(2007/10/02)
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- Synthesis of Novel Citrate-Based Siderophores and Siderophore-β-Lactam Conjugates. Iron Transport-Mediated Drug Delivery Systems
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The synthesis of analogs of arthrobactin (5), a microbial iron chelator, and its imide 8 are described.The differentially protected citric acid residue 31 served as the key intermediate in making conjugates having a generalized structure 14 with two representative carbacephalosporin units, 15 and 16.Both conjugates, 49 and 51, showed antibiotic activity, while conjugate 51 obtained from β-lactam 16 bearing a phenylglycyl side chain was shown to be more effective.
- Ghosh, Arun,Miller, Marvin J.
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p. 7652 - 7659
(2007/10/02)
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