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Peter Gebhardt

Publications and source records attributed to Peter Gebhardt.

7 recordsLinked to original sources
PubMed2006

An unusual reaction of the natural compound benaphthamycin B: theoretical study of a model system.

The surprising and complex transformation of benaphthamycin B to give quinone 2a is investigated theoretically with a model compound, 1,5-dihydroxy-4-methoxy-2,3-dimethylanthraquinone (3). The detailed study is performed using both DFT and perturbation theory under inclusion of solvent effects. Several individual steps (reduction and hydrolysis, water elimination, ether cleavage, and oxidation) of the proposed reaction cascade calculated at the PCM-MP2/6-31G(d)//B3LYP/6-31G(d) level of theory are presented and discussed. It is shown that the key step, the ether cleavage as an S(N)2 reaction leading to the anthrone 12a, possesses a smaller activation barrier compared to the alternative process yielding 12b. Therefore, the formation of the thermodynamically preferred model quinone 13a is also the kinetically favored pathway: The results of the calculated model reaction should also be valid for benaphthamycin B (1).

Benz(a)Anthracenes↗
PubMed2005

The expression of selected non-ribosomal peptide synthetases in Aspergillus fumigatus is controlled by the availability of free iron.

Three non-ribosomal peptide synthetase genes, termed sidD, sidC and sidE, have been identified in Aspergillus fumigatus. Gene expression analysis by RT-PCR confirms that expression of both sidD and C was reduced by up to 90% under iron-replete conditions indicative of a likely role in siderophore biosynthesis. SidE expression was less sensitive to iron levels. In addition, two proteins purified from mycelia grown under iron-limiting conditions corresponded to SidD ( approximately 200 kDa) and SidC (496 kDa) as determined by MALDI ToF peptide mass fingerprinting and MALDI LIFT-ToF/ToF. Siderophore synthetases are unique in bacteria and fungi and represent an attractive target for antimicrobial chemotherapy.

Aspergillus fumigatus↗
PubMed2005

Efficient synthesis of 9- and 13-oxo leucomycin derivatives using hypervalent iodine reagents in solution and on solid support.

An efficient procedure for the highly selective oxidation of leucomycines to the corresponding 16-membered 9- and 13-oxo macrolides using hypervalent iodinates is presented. Both the Dess-Martin periodinane (DMP) and polymer-bound 2-iodoxybenzoic acid (IBX) show clear advantages over the previously employed manganese dioxide. Key intermediates for a variety of further chemical derivatization methods (2a, 2b) are obtained in very good yields without the requirement of protecting groups.

Catalysis↗
PubMed2003

Fe(III) coordination properties of a new saccharide-based exocyclic trihydroxamate analogue of ferrichrome.

The coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl-2,3,4-tris-O-[4-(N-hydroxy-N-methylcarbamoyl)-n-butyrate]-alpha-d-glucopyranoside (H(3)L), is reported, along with its pK(a) values, Fe(III) and Fe(II) chelation constants, and aqueous-solution speciation as determined by spectrophotometric and potentiometric titration techniques. The use of a saccharide platform to synthesize a hexadentate trihydroxamic acid chelator provides some advantages over other approaches to ferrichrome models, including significant water solubility and hydrogen-bonding capability of the backbone that can potentially provide favorable receptor recognition and biological activity. The pK(a) values for the hydroxamate moieties were found to be similar to those of other trihydroxamates. Proton-dependent Fe(III)-H(3)L and Fe(II)-H(3)L equilibrium constants were determined using a model involving the sequential protonation of the iron(III)- and iron(II)-ligand complexes. These results were used to calculate the formation constants, log beta(110) = 31.86 for Fe(III)L and 12.1 for Fe(II)L(-). The calculated pFe value of 27.1 indicates that H(3)L possesses an Fe(III) affinity comparable to or greater than those of ferrichrome and other ferrichrome analogues and is thermodynamically capable of removing Fe(III) from transferrin. E(1/2) for the Fe(III)L/Fe(II)L(-) couple was determined to be -436 mV from quasi-reversible cyclic voltammograms at pH = 9, and the pH-dependent E(1/2) profile was used to determine the Fe(II)L(-) protonation constants.

Algorithms↗
PubMed2003

Trishydroxamates and triscatecholates based on monosaccharides and myo-inositol as artificial siderophores.

New trishydroxamates and triscatecholates based on methyl alpha-D-glucopyranoside, methyl alpha-D-galactopyranoside, methyl alpha-D-ribopyranoside and methyl alpha-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.

Catechols↗
PubMed2002

New synthetic catecholate-type siderophores with triamine backbone.

New analogues of triscatecholate siderophores based on linear or tripodal triamines with or without spacer groups or lipophilic and hydrophilic substituents were synthesized. The catecholate moieties were prepared in OH-forms, as acetylated compounds or masked as 8-methoxycarbonyloxy-2,4-dioxo-1,3-benzoxazine derivatives. Some of the new compounds were active as siderophores tested by growth promotion assays using various gram-negative bacteria and mycobacteria under iron limitation and by CAS-assay. Structure-activity-correlations have been studied.

Amines↗