Hydroxamic acids siderophores

Bisucaberin (48) from Alteromonas haloplanktis (181) is a cyclic dimer of succinyl-((V-hydroxycadaverin) (348) cf. the cyclic trimer proferrioxamine E (Table 6). 

In putrebactin from Shewanella putrefaciens (201) cadaverine is replaced by pufrescine (49, R = H). For the cyclic trimer, see proferrioxamine X2 in Table 6. The arctic S. gelidimarina living in a habitat with extremely low iron supply produces a cell-associated hydroxamic acid siderophore with the mass 977 Da for of unknown structure (274). 

Alcaligin from Alcaligenes denitrificans (260) and from Bordetella spp. (244) is a cyclic dimer of succinyl-V 3S-dihydroxyputrescine (49, R = H) confirmed by synthesis (402). 

Structures were not established for C and F (7 values and physical constants) (iOd), T4-T6, and Xg, X9 (mass spectra) 115) 

Alcaligin E from Alcaligenes eutrophus is described from color tests as a phenolic siderophore (126a). According to a recent publication (90a) it is identical with staphyloferrin B, a citrate siderophore (Sect. 4.2). No further information is given to resolve these discrepancies. 

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Fig. 19. Plot of redox potentials (Ey2) as a function of pFe3+ values for a series of hexadentate, tetradentate, and bidentate hydroxamic acid siderophores and siderophore mimics. Data from Table V. Legend 1 — ferrioxamine E 2 — ferrioxamine B (4) 3 — H.aLjf4 (11) 4 — H >L 36 (12) 5 - coprogen 6 - ferricrocin 7 - ferrichrome (6) 8 - alcaligin 9 -rhodotorulic acid (3) 10 — NMAHA 11 — AHA 12 — Ly-AHA.

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

Fig. 1. Common siderophore iron-binding groups catechol (Eq. (4)), hydroxamic acid (Eq. (5)), ot-hydroxycarboxylic acid (Eq. (6)), and hydroxypyridinone (Eq. (7)). Additional siderophore binding groups ...

Fig. 6. Saccharide-platform siderophore mimics with catechol and hydroxamic acid donor groups, H6L 34(9), H6Lg34(10), H3L 34(11), and H3L236(12).

Exochelins (322,323) are peptidic siderophores imm Mycobacterium spp. (see also below mycobactins). Exochelin MS (16) from M. smegmatis comprises (3-Ala and three W -OHOm units, which are linked by their atoms to acyl groups thus forming hydroxamic acids. 

Fig. 15. Citrate siderophores with two hydroxamic acid units...

The A-hydroxycarboxamide group is a key fragment of many siderophores so that a convenient synthesis of this group is crucial for further progress. A variety of methods have been attempted for the preparation of hydroxamic acids starting from carboxylic acids. Although some of these methods are quite efficient for the preparation of substituted hydroxamic acids, the preparation of the parent compound is still a problem and yields are often moderately unacceptable, in part due to the low solubility of the parent hydroxylamine hydrochloride in organic solvents. 

Natural and biomimetic hydroxamic acid based siderophores... 

In this chapter, we wiU concentrate mainly on hydroxamate-based siderophores. However, the most representative example of the catechol-based siderophore family is entero-bactin , a highly Cs-symmetric molecule based on a trilactone ring system derived from three L-serine amino acids. The serine amino groups are extended with three catecholic acid units. Enterobactin binds iron(III) in an octahedral coordination of preferred A-cis configuration (see Figure 1 in Section n.C). 

V. NATURAL AND BIOMIMETIC HYDROXAMIC ACID BASED SIDEROPHORES A. The Major Hydroxamate Siderophore Families and Their Analogs... 

Natural and biomimetic hydroxamic acid based siderophores TABLE 2. Natural ferrioxamines and their structural variations... 

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