153492-09-2Relevant articles and documents
Endo-Hydroxamic Acid Monomers for the Assembly of a Suite of Non-native Dimeric Macrocyclic Siderophores Using Metal-Templated Synthesis
Brown, Christopher J. M.,Gotsbacher, Michael P.,Holland, Jason P.,Codd, Rachel
, p. 13591 - 13603 (2019)
An expedited synthesis of endo-hydroxamic acid aminocarboxylic acid (endo-HXA) compounds has been developed. These monomeric ligands are relevant to the synthesis of metal-macrocycle complexes using metal-templated synthesis (MTS), and the downstream production of apomacrocycles. Macrocycles can display useful drug properties and be used as ligands for radiometals in medical imaging applications, which supports methodological advances in accessing this class of molecule. Six endo-HXA ligands were prepared that contained methylene groups, ether atoms, or thioether atoms in different regions of the monomer (1-6). MTS using a 1:2 Fe(III)/ligand ratio furnished six dimeric hydroxamic acid macrocycles complexed with Fe(III) (1a-6a). The corresponding apomacrocycles (1b-6b) were produced upon treatment with diethylenetriaminepentaacetic acid (DTPA). Constitutional isomers of the apomacrocycles that contained one ether oxygen atom in the diamine-containing (2b) or dicarboxylic acid-containing (3b) region were well resolved by reverse-phase high-performance liquid chromatography (RP-HPLC). Density functional theory calculations were used to compute the structures and solvated molecular properties of 1b-6b and showed that the orientation of the amide bonds relative to the pseudo-C2 axis was close to parallel in 1b, 2b, and 4b-6b but tended toward perpendicular in 3b. This conformational constraint in 3b reduced the polarity compared with 2b, consistent with the experimental trend in polarity observed using RP-HPLC. The improved synthesis of endo-HXA ligands allows expanded structural diversity in MTS-derived macrocycles and the ability to modulate macrocycle properties.
Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group
Wu, Tom Y. H.,Hassig, Christian,Wu, Yiqin,Ding, Sheng,Schultz, Peter G.
, p. 449 - 453 (2007/10/03)
Histone deacetylases (HDAC) are promising targets for cancer chemotherapy. HDAC inhibitors are thought to act in part by disrupting normal cell cycle regulation, resulting in apoptosis and/or differentiation of transformed cells. Several HDAC inhibitors,
Method for preparing desferrioxamine B and homologs thereof
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, (2008/06/13)
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
A versatile synthesis of deferrioxamine B
Bergeron,McManis,Phanstiel IV,Vinson
, p. 109 - 114 (2007/10/02)
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.
Synthesis of Novel Citrate-Based Siderophores and Siderophore-β-Lactam Conjugates. Iron Transport-Mediated Drug Delivery Systems
Ghosh, Arun,Miller, Marvin J.
, p. 7652 - 7659 (2007/10/02)
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.
