Regioselective Palladium(0) Catalyzed Amination of Carbonates of Allylic α-Hydroxyphosphonates with Hydroxylamine Derivatives: A Convenient Route to Phosphonic Acids Related to the Antibiotic Fosmidomycin

Öhler, Elisabeth; Kanzler, Silvia

doi:10.1055/s-1995-3942

Cited by 39 publications

(12 citation statements)

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“…4-[2-methyl,2- C 5 ]methylerythritol cyclopyrophosphate were kindly provided by W. Eisenreich, TU Mü nchen, Germany. Fosmidomycin was synthesized according to published methods (17,18). All intermediates were characterized using 1 H and 13 C NMR spectroscopy; the final product additionally was analyzed by ESI-MS.…”

Section: Methodsmentioning

confidence: 99%

Escherichia coli Produces Phosphoantigens Activating Human γδ T Cells

Feurle

Espinosa

Eckstein

et al. 2002

Journal of Biological Chemistry

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Human V␥9␦2 T lymphocytes are suggested to play an important role in the immune response to various microbial pathogens. In contrast to ␣␤ T cells, ␥␦ T lymphocytes recognize small, non-protein, phosphate-bearing antigens (phosphoantigens) in a major histocompatibility complex-independent manner. Four different phosphoantigens termed TUBag1 to TUBag4 with a common 3-formyl-1-butyl-pyrophosphate moiety and isopentenyl-pyrophosphate have been isolated and identified from mycobacteria. However, natural occurring ␥␦ T cell ligands from other bacterial species were not characterized so far. Here, we describe the structural identification of the two compounds responsible for the ␥␦ T cell-stimulating capacity of Escherichia coli as similar to the mycobacterial phosphoantigens 3-formyl-1-butylpyrophosphate and its M r 275 homologue TUBag2. In addition, E. coli phosphoantigens exert bioactivities on ␥␦ T cells with similar potencies to the mycobacterial phosphoantigens at 5-15 nM concentration. Furthermore, our results clearly prove that the deoxyxylulose 5-phophate pathway (also referred to as Rohmer metabolic route of isoprenoid biosynthesis) is essential for the biosynthesis of the phosphoantigens in E. coli. Because this pathway is absent from human cells, it proves an ideal target for focusing efficiently the antimicrobial selectivity of human ␥␦ T lymphocytes.

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Section: Methodsmentioning

confidence: 99%

Escherichia coli Produces Phosphoantigens Activating Human γδ T Cells

Feurle

Espinosa

Eckstein

et al. 2002

Journal of Biological Chemistry

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“…FR-900098 was synthesised by a combination of the protocols reported by Kamiya et al [39] and Öhler and Kanzler. [40] The expression vector pQE60, the repressor plasmid pREP4 and the E. coli strain XL1-Blue were sourced from Qiagen. The vitamin supplement (Difco Yeast Nitrogen Base) was obtained from BD (Heidelberg, Germany), and Standard I medium was from Roth (Karlsruhe, Germany).…”

Section: Discussionmentioning

confidence: 99%

NMR Studies of DOXP Reductoisomerase and its Inhibitor Complex

Englert¹,

Richter²,

Wiesner³

et al. 2011

ChemBioChem

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1-Deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase (EC1.1.1.267) catalyses the second step of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis. The enzyme is used by most bacteria, apicomplexan parasites and the plastids of plants, but not by humans, and therefore represents an attractive target for antibacterial, antiparasitic and herbicidal compounds. Fosmidomycin, an inhibitor of DXR, has been found to be active against bacterial infections and malaria in early clinical studies. Here, we report sample optimisation, partial backbone assignment and secondary-structure prediction of E. coli DXR by heteronuclear NMR analysis for further NMR-aided drug discovery. Perdeuterated (15)N,(13)C-labelled samples were prepared under oxygen exclusion in the presence of Mg(2+), NADPH and the inhibitor FR-900098, a close derivative of fosmidomycin. (1)H and (15)N backbone assignment was achieved for 44 % of the primary structure, and (13)C backbone assignment was achieved for 50 % of the primary structure. Comparison with previously solved crystal structures revealed that the assigned fragments were located mainly in helical regions on the solvent-exposed surface of the enzyme. Torsion angle likelihood obtained from shift and sequence similarity (TALOS) was used for secondary structure prediction, resulting in agreement with eight available crystal structures; deviations could be observed for the catalytic loop region.

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“…5,6,7 Another route describes the palladium catalyzed amination with N,O-protected hydroxylamine derivatives of phosphonylated allylic carbonates. 8,9,10 A similar route was described by Genet 11 et al by palladium catalyzed alkylations of diethyl aminomethylphosphonate Schiff bases to prepare unsaturated α-aminophosphonates. A slightly different approach describes the palladium catalyzed reaction of 3-acetoxy-1-alkenyl phosphonates with ethyl diphenyl methylene amino…”

Section: Introductionmentioning

confidence: 93%