title: Diphenyl-benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester: a convenient catechol precursor in the synthesis of siderophore vectors suitable for antibiotic Trojan horse strategies.
abstract: Catechols are components of many metal-chelating compounds, including siderophores that are naturally occurring iron(III) chelators excreted by microorganisms. Catechol derivatives are poorly soluble in organic media and the synthesis of catechol-containing molecules requires the use of protected catechol precursors with improved organic solubility. We therefore developed 2,2-diphenyl-benzo[1,3]dioxole-4-carboxylic acid pentafluorophenyl ester. This activated ester reacts with an amine functionalized scaffold to generate chelators in which the catechol functions are protected in the form of diphenyl-benzodioxole moieties. The catechol can subsequently be deprotected, at the end of the synthesis, with trifluoroacetic acid (TFA). This strategy was applied to the synthesis of two catechol compounds functionalized with a terminal propargyl extension. These two compounds were shown to promote iron uptake in Escherichia coli and Pseudomonas aeruginosa. These two compounds are suitable for use as vectors in antibiotic Trojan horse approaches, as they could be conjugated with azide-functionalized antibiotics using the Huisgen dipolar 1,3-cycloaddition.
authors.affiliation: Team "Transports Membranaires Bactériens", UMR 7242 Université de Strasbourg-CNRS. Boulevard Sébastien Brant, 67400 Illkirch, France. mislin@unistra.fr.
authors.forename: Etienne
authors.initials: E
authors.lastname: Baco
authors.forename: Françoise
authors.initials: F
authors.lastname: Hoegy
authors.forename: Isabelle J
authors.initials: IJ
authors.lastname: Schalk
authors.forename: Gaëtan L A
authors.initials: GL
authors.lastname: Mislin
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry*; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004149:Dioxoles / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007501:Iron / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism; D017262:Siderophores / Q000737:chemistry*; D005466:Fluorocarbons
chemical_list: D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D002396:Catechols; D004149:Dioxoles; D006845:Hydrocarbons, Fluorinated; D007501:Iron; D017262:Siderophores; C000592075:diphenyl-benzo(1,3)dioxole-4-carboxylic acid pentafluorophenyl ester; D005466:Fluorocarbons; C034221:catechol