Hydroxamate containing siderophores

The first synthesis of a siderophore was the preparation of ferrioxamine B over 20 years ago in order to confirm the chemical structure of this natural product67). Synthesis of the other hydroxamate containing siderophores has as a central problem preparation of the constituent to-N-hydroxy amino acid in an optically pure form. The most important such subunit in hydroxamate siderophores is Ns-hydroxy ornithine. This is a chiral building block of the diketopiperazine-containing siderophores (rhodo-torulic acid 68), dimerum acid 69), coprogen 70) and coprogen B 69>), the cyclic hexa-peptides of the ferrichrome family27), the fusarinines 71 -73) and the antibiotic ferri-chrome derivatives albomycines Sl5 S2 and e 61-62). 

Bergeron RJ, Phanstiel O (1992) The total synthesis of nannochelin a novel cinnamoyl hydroxamate - containing siderophores. J Org Chem 57 7140-7143... 

The second main class of Fem-specific sequestering agents (siderophores) responsible for the acquisition and assimilation of iron employ hydroxamate ligating groups (34).157158 186 Two important subclasses are the ferrioxamines and the ferrichromes (Figure 5). Examples are ferrioxamine B, a linear trihydroxamic acid and ferrichrome A, a cyclic hexapeptide carrying three hydroxamate-containing side chains. 

Hydroxamate- or catecholate-containing siderophores are strongly absorbing species with characteristic spectra (see Table 1) which can be utilized for spectrophotometric determination of the complex formation constant. Iron(III) hydroxamates absorb in the visible region, producing a broad absorption band in the 420-440 nm region. Iron(III) catecholates exhibit pH-dependent absorption maxima. Unfortunately, the overall Fe + ion complex formation constants cannot be determined directly at neutral pH, because the extremely high stability of siderophore complexes precludes direct measurements of the equilibrium of interest, which would yield the desired formation constant for a tris-bidentate siderophore complex, /3no (equation (2)). ... 

A hydroxamate siderophore from Salmonella typhimurium is described as containing isoleucine/leucine, phenylalanine and valine, but not serine and lysine. Further details are not given (290a). For other Salmonella siderophores see Sect. 2.7. 

A multiple-path mechanism has been elaborated for dissociation of the mono- and binuclear tris(hydroxamato)-iron(III) complexes with dihydroxamate ligands in aqueous solution. " Iron removal by edta from mono-, bi-, and trinuclear complexes with model desferrioxamine-related siderophores containing one, two, or three tris-hydroxamate units generally follows first-order kinetics though biphasic kinetics were reported for iron removal from one of the binuclear complexes. The kinetic results were interpreted in terms of discrete intrastrand ferrioxamine-type structures for the di-iron and tri-iron complexes of (288). " Reactivities for dissociation, by dissociative activation mechanisms, of a selection of bidentate and hexadentate hydroxamates have been compared with those of oxinates and salicylates. ... 

Azotobactin is a highly fluorescent hexadentate mixed siderophore containing a pyoverdin-like bidentate ligating chromophore, derived from 2,3-diamino-6,7-dihydroxyquinoline, a hydroxamate and a a-hydroxycarboxylic acid for Fe(in) coordination. ... 

The first known siderophore, isolated in 1952 by Neilands,22 is ferrichrome (Fig. 16-1), a cyclic hexa-peptide containing hydroxamate groups at the ironbinding centers. Oxygen atoms form the bonds to iron... 

The isomers of Cr(men)3 isomerize with half-lives (several hours) similar to the Cr(benz)3 complex. The rate of isomerization of the tris-(hydroxamate) complexes is therefore not particularly sensitive to the substituent of the hydroxamate nitrogen atom, since the men ligand contains an alkylated nitrogen atom, and the benz ligand contains an unsubstituted nitrogen atom. In the absence of an induced strain, the corresponding siderophore complexes must isomerize much more slowly because of the steric constraints of the ligand. 

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