Abstract
New trishydroxamates and triscatecholates based on methyl α-D-glucopyranoside, methyl α-D-galactopyranoside, methyl α-D-ribopyranoside and methyl α-D-xylopyranoside as well as on 1,3,5-tri-O-benzyl-myo-inositol were synthesized. N-Methylsuccinohydroxamate, N-methylglutarohydroxamate and their O-benzoyl derivatives were used as hydroxamate moieties. 2,3-Dihydroxybenzoyl derivatives and acylated compounds as well as 2,3- and 3,4-dihydroxybenzylidenehydrazino derivatives, partly with spacer groups, were utilized as catecholate components. The siderophore activity of the prepared siderophore analogues was examined by a growth promotion assay with various Gram-negative bacteria and mycobacteria and by the CAS-assay. Some trishydroxamates and triscatecholates showed siderophore activity on Gram-negative bacteria and triscatecholates on mycobacteria. Iron complexes of the trishydroxamates act as siderophores for all types of iron transport mutants. The recognition and uptake specificity of these compounds was studied by E. coli siderophore receptor and iron transport mutants. Structure activity correlations are discussed.
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References
Bazin H, Bouchu A, Descotes G. 1995 Hydrolysis of cyanoethylated carbohydrates: syntheses of new carboxylic derivatives of sucrose, D-glucose and D-fructose. J Carbohydr Chem 14, 1187–1207.
Bergeron RJ, McGovern KA, Channing MA, Burton PS. 1980 Synthesis of N 4-Acylated N 1, N 8-Bis(acyl)spermidines: An approach to the synthesis of siderophores. J Org Chem 45, 1589–1592.
Bergeron RJ, Wiegand J, Brittenham GM. 1999 HBED: The continuing development of a potential alternative to deferroxamine for iron-chelating therapy. Blood 93, 370–375.
Billington DC, Baker R, Kulagowski JJ, Mawer IM. 1989 The total synthesis of myo-inositol phosphates via myo-inositol orthoformate. J Chem Soc Perkin Trans I, 1423–1429.
Bishop CT, Cooper FP. 1963 Glycosidation of sugars: II. Methanolysis of D-Xylose, D-Arabinose, D-Lyxose, and D-Ribose. Can J Chem 41, 2743–2758.
Budzekiewicz H. 2001 Siderophore-antibiotic conjugates used as trojan horses against Pseudomonas aeruginosa. Curr Topics Med Chem 1, 73–82.
Chaudhary S, Hernandez O. 1979 A simplified procedure for the preparation of triphenylmethylethers. Tetrahedr Lett 2, 95–98.
Coleman AW, Lin CC, Miocque M. 1992 Synthese und Komplexierungsverhalten eines auf Cyclodextrin beruhenden Siderophors. Angew Chem 104, 1402–1404.
Dax K, Wolfleiner W, Weidmann H. 1978 Eine einfache Enttritylierungsmethode. Carbohydr Res 65, 132–138.
Dhungana S, Heggemann S, Heinisch L, Möllmann U, Boukhalfa H, Crumbliss AL. 2001 Fe(III) coordination properties of two new saccharide-based enterobactin analogues: Methyl 2,3,4-Tris-O-N-[2,3-di(hydroxy)benzoylglycyl]-aminopropyl-α-D-glucopyranoside and Methyl 2,3,4-Tris-O-N-[2,3-di-(hydroxy)-benzoyl]-aminopropyl-α-D-glucopyranoside. Inorg Chem 40, 7079–7086.
Dhungana S, Heggemann S, Gebhardt P, Möllmann U, Boukhalfa H, Crumbliss AL. 2002 Fe(III) coordination properties of a new saccharide based exocyclic trihydroxamate analogue of ferrichrome. Inorg Chem (in press).
Drechsel H, Jung G. 1998 Peptide siderophores. J Peptide Sci 4, 147–181.
Hall MJ, Ratledge C. 1982 A simple method for the production of mycobactin, the lipid-soluble siderophore, from mycobacteria. FEMS Microbiol Lett 15, 133–136.
Hantke K. 1990 Dihydroxybenzoylserine, a siderophore for E. coli. FEMS Microbiol Lett 67, 5–8.
Heggemann S, Schnabelrauch M, Klemm D, Möllmann U, Reissbrodt R, Heinisch L. 2001 New artificial siderophores based on a monosaccharide scaffold. BioMetals 14, 1–11.
Heinisch L, Gebhardt P, Heidersbach R, Reissbrodt R., Möllmann U. 2002a New synthetic catecholate-type siderophores with triamine backbone. BioMetals 15, 133–144.
Heinisch L, Wittmann S, Stoiber T, Berg A, Ankel-Fuchs D, Möllmann U. 2002b Highly antibacterial active aminoacylpenicillin conjugates with bis-catecholate siderophores based on secondary diamino acids and related compounds. J Med Chem 45, 3032–3040.
Mori K. 1974 Synthesis of exo-Brevicomin, the Pheromone of Western Pine Beetle, to obtain optically active forms of known absolute configuration. Tetrahedron 30, 4223–4227.
Mowery jr. DW. 1963 Methyl-D-Mannosides. Meth Carbohydr Chem 2, 328–331.
Neises B, Steglich W. 1978 Ein einfaches Verfahren zur Veresterung von Carbonsäuren. Angew Chemie 90, 556–557.
Pradines B, Ramiandrasoa F, Basco LK, Bricard L, Kunesch G, Le-Bras J. 1996 In vitro activities of novel catecholate siderophores against Plasmodium falciparum. Antimicrob Ag Chemother 40, 2094–2098.
Rastetter WH, Erickson TJ, Venuti MC. 1981 Synthesis of iron chelators. Enterobactin, enantioenterobactin, and chiral analogue. J Org Chem 46, 3579–3590.
Reissbrodt R, Heinisch L, Möllmann U, Rabsch W, Ulbricht H. 1993 Growth promotion of synthetic catecholate derivatives on Gram-negative bacteria. BioMetals 6, 155–162.
Rosenmund KW, Boehm T. 1926 Zur Kenntnis der Polyoxo-Benzylalkohole, insbesondere des Gallusalkohols und eines daraus gewonnenen Gerbstoffs. Arch Pharm 457, 448–459.
Rotheneder A, Fritsche G, Heinisch L., Möllmann U, Heggemann S, Larcher C, Weiss G. 2002 Effects of synthetic siderophores on proliferation of Plasmodium falciparum in infected human erythrocytes. Antimicrob Ag Chemother 46, 2010–2013.
Schnabelrauch M, Egbe DAM, Heinisch L, Reissbrodt R, Möllmann U. 1998 Novel catecholate-type siderophore analogues based on a myo-inositol scaffold. BioMetals 11, 243–251.
Schumann G, Möllmann U. 2001 Screening system for xenosiderophores as potential drug delivery agents in mycobacteria. Antimicrob Ag Chemother 45, 1317–1322.
Schumann G, Möllmann U, Heinemann I. 1998 Mutants of Mycobacterium species and their use for screening of antibiotic vectors. Patent application DE 19817021.9. (17.4.1998).
Schwyn B, Neilands JB. 1987 Universal chemical assay for the detection and determination of siderophores. Anal Biochem 160, 47–56.
Sharma SK, Miller MJ, Payne SM.1989 Spermaxatin and Spermaxatol: New synthetic spermidine-based siderophore analogues. J Med Chem 32, 357–367.
Tse B, Kishi Y. 1993 Chiral analogues of enterobactin with hydrophilic or lipophilic properties. JA Chem Soc 115, 7892–7893.
Wittmann S, Schnabelrauch M, Scherlitz-Hofmann I, Möllmann U, Ankel-Fuchs D, Heinisch L. 2002 New synthetic siderophores and their ?-lactame conjugates based on diamino acids and dipeptides. Bioorg Med Chem 10, 1659–1670.
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Heggemann, S., Möllmann, U., Gebhardt, P. et al. Trishydroxamates and triscatecholates based on monosaccharides and myo-inositol as artificial siderophores. Biometals 16, 539–551 (2003). https://doi.org/10.1023/A:1023476214838
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DOI: https://doi.org/10.1023/A:1023476214838