88109-07-3Relevant articles and documents
A much improved synthesis of the siderophore enterobactin
Ramirez, Robert J. A.,Karamanukyan, Levon,Ortiz, Steven,Gutierrez, Carlos G.
, p. 749 - 752 (1997)
Enterabadin, the cyclic trimer of N-(2,3-dihydroxybenzoyl)-L-serine has been efficiently prepared. A simple and high yield procedure has been developed for construction of N-protected serine trilactone as the key intermediate: methyl N-trityl-L-serinate and 2,2-dibutyl-1,3,2-dioxastannolane were refluxed in xylene to produce the triolide as the only lactone product in 85% yield.
Oxinobactin and sulfoxinobactin, abiotic siderophore analogues to enterobactin involving 8-hydroxyquinoline subunits: Thermodynamic and structural studies
Du Moulinet D'Hardemare, Amaury,Gellon, Gisele,Philouze, Christian,Serratrice, Guy
, p. 12142 - 12151 (2013/01/15)
The synthesis of two new iron chelators built on the tris-l-serine trilactone scaffold of enterobactin and bearing a 8-hydroxyquinoline (oxinobactin) or 8-hydroxyquinoline-5-sulfonate (sulfoxinobactin) unit has been described. The X-ray structure of the ferric oxinobactin has been determined, exhibiting a slightly distorted octahedral environment for Fe(III) and a Δ configuration. The Fe(III) chelating properties have been examined by potentiometric and spectrophotometric titrations in methanol-water 80/20% w/w solvent for oxinobactin and in water for sulfoxinobactin. They reveal the extraordinarily complexing ability (pFeIII values) of oxinobactin over the p[H] range 2-9, the pFe value at p[H] 7.4 being 32.8. This was supported by spectrophotometric competition showing that oxinobactin removes Fe(III) from ferric enterobactin at p[H] 7.4. In contrast, the Fe(III) affinity of sulfoxinobactin was largely lower as compared to oxinobactin but similar to that of the ligand O-TRENSOX having a TREN backbone. These results are discussed in relation to the predisposition by the trilactone scaffold of the chelating units. Some comparisons are also made with other quinoline-based ligands and hydroxypyridinonate ligand (hopobactin).
High-yield synthesis of the enterobactin trilactone and evaluation of derivative siderophore analogs
Meyer,Telford,Cohen,White,Xu,Raymond
, p. 10093 - 10103 (2007/10/03)
A novel one-step synthesis of the macrocyclic triserine trilactone scaffold of the siderophore enterobactin, which eliminates the β-lactonization step of N-tritylserine, is presented. The cyclization reaction is based on a stannoxane template and leads to an overall yield of ~ 50%. This enables the practical functionalization of the trilactone by attaching chelating groups other than catecholamides. The conformational stability of the trilactone ring has been examined by high-resolution X-ray diffraction studies of the N-trityl intermediate: crystals grown from methylene chloride:methanol are orthorhombic, space group P212121 With unit cell dimensions a = 9.2495(5) A?, b = 11.3584(1) A?, c = 48.945(1) A?, V = 5142.1(2) A?3, and Z = 4. A hydroxypyridinonate analog of enterobactin, N,N',N''-tris[(3-hydroxy-1-methyl-2-oxo-(1H-pyridinyl)carbonyl]-4-cyclotriseryl trilactone (hopobactin), has been prepared by attachment of three 3-hydroxy-1-methyl-2(1H)-pyridinonate (3,2-HOPO) moieties to the triserine trilactone. This ligand represents the first enterobactin analog that retains the trilactone scaffold, but employs chelates other than catecholamides. Crystals of the chiral ferric complex grown from DMF:diethyl ether are monoclinic, space group P21, with unit cell dimensions a 13.0366(9) A?, b = 22.632(2) A?, c = 27.130(2) A?, b = 100.926(1)(o), V = 7860(1) A?3, and Z = 8. The Δ configuration of enterobactin metal complexes is also enforced in those of hopobactin and persists in aqueous or methanolic solution, as demonstrated by circular dichroism. The ferric hopobactin complex is the first reported chiral complex of hydroxypyridinonate ligands. The solution coordination chemistry of this new ligand and its iron(III) and iron(II) complexes have been studied by means of 1H NMR, potentiometric, spectrophotometric, and voltammetric methods. The average protonation constant of the hopobactin free ligand (log K(av) = 6.1) is typical of other 3-hydroxy-1-methyl-2-oxo-1H-pyridin-4-carboxamide ligands. The stability constants of the iron(III) complex formed with hopobactin (log β110 = 26.4) and with the tris(2-aminoethyl)amine-based analog, TRENHOPO, (log β110 to = 26.7) are of the same order of magnitude, unlike the catecholamide-based species, where enterobactin (log β110 = 49) is 6 orders of magnitude more stable than TRENCAM (log β110 = 43.6). The stability enhancement reflects the specific predisposition by the triserine scaffold of the catecholamide binding units. In spite of a significantly lower affinity of 3,2-hydroxypyridinonates for iron(III) compared with the more basic catecholates, hopobactin is an extraordinarily powerful chelating agent under acidic conditions: No measurable dissociation is observed even in 1.0 M HCl. In contrast to enterobactin and its synthetic derivatives, the hopobactin ferric complex undergoes no sequential protonation above pH 1. The affinity of hopobactin and TRENHOPO for iron(III) relative to iron(II) results in strongly negative reduction potentials, -782 mV vs 0.01 M Ag+/Ag in CH3CN or -342 mV vs NHE in water and -875 mV vs 0.01 M Ag+/Ag in CH3CN or -435 mV vs NHE in water, respectively.
