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Biomedical subjects

Franz Bracher

Publications and source records attributed to Franz Bracher.

12 recordsLinked to original sources
PubMed2006

Multiresidue analytical method using dispersive solid-phase extraction and gas chromatography/ion trap mass spectrometry to determine pharmaceuticals in whole blood.

A convenient analytical method for the simultaneous determination of more than 40 pharmaceuticals belonging to various therapeutic categories in whole blood has been developed. Exemplarily, the method was fully validated for eight different pharmaceuticals. The procedure entails addition of acetonitrile, magnesium sulfate and sodium chloride to a small amount of blood, then the mixture is shaken intensively and centrifuged for phase separation. An aliquot of the organic layer is cleaned up by dispersive solid-phase extraction employing bulk sorbents as well as magnesium sulfate for the removal of residual water. This method was based on the QuEChERS approach developed for pesticide residue analysis in food. Gas chromatography/ion trap mass spectrometry (GC/MS) with electron (EI) and chemical (CI) ionisation was then used for qualitative and quantitative determination of the pharmaceuticals. The dispersive SPE with PSA (sorbent functionalized with primary and secondary amines) was found more suitable than aminopropyl and a styrene-divinylbenzene sorbent for sample clean-up before drug level determination in whole blood and plasma, as it was found that most of endogenous matrix components were removed and the analytes were isolated from spiked samples with recoveries above 80%. Variation coefficients of the repeatability typically smaller than 10% have been achieved for a wide range of the investigated substances. The used analytical conditions allowed to separate successively a variety of drugs and poisons with the typical limit of detection at <20 ng mL(-1) levels using 1 microL injection of equivalent blood sample in whole blood. The method is simple, rapid, cheap and very effective for therapeutic drug monitoring and forensic chemistry.

Absorption↗
PubMed2005

Short and efficient approach towards macrocyclic lactones based on a Sonogashira reaction.

Polyketide-derived macrolactones like zearalenone (1), zearalane (2) or curvularin (3) display a wide range of interesting pharmacological activities. Here, we present a short and efficient approach towards this class of natural products by a combination of the Sonogashira and Mitsunobu reactions. The resulting lactone 9 was tested against human cancer cell lines at the NCI.

Antineoplastic Agents↗
PubMed2004

Saludimerines A and B, novel-type dimeric alkaloids with stereogenic centers and configurationally semistable biaryl axes.

The first biarylic bis-morphinanedienone alkaloids, saludimerines A (3a) and B (3b), isolated from a tree of Croton flavens (Euphorbiaceae) are described. These naturally occurring dimers of the known alkaloid salutaridine are joined together via a rotationally hindered biaryl axis, giving rise to atropo-diastereomers that are configurationally stable at room temperature but slowly interconvert in methanolic solution within several days. Their structures were established by spectroscopic methods and by partial synthesis, which was achieved by a highly atropo-diastereoselective biomimetic oxidative coupling of the monomeric precursor, salutaridine. Their axial configurations were elucidated by circular dichroism (CD) investigations, which succeeded despite the fact that the two atropo-diastereomers exhibit near-identical CD spectra. This remarkable phenomenon was rationalized by quantum chemical CD calculations. The configurational assignment of saludimerines A (3a) as P-axial and B (3b) as M was corroborated by atropisomer-specific NOE interactions between protons of the one molecular half with nuclei in the other.

Alkaloids↗
PubMed2004

New total synthesis of niphatesine C and norniphatesine C based on a Sonogashira reaction.

The pyridine alkaloid niphatesine C and its analogue norniphatesine C were prepared in a short and efficient way starting from commercially available 3-iodopyridine and undec-10-yn-1-ol using a Sonogashira reaction as the key step. The resulting alkylpyridines were tested for antimicrobial activity against several bacteria and fungi. The cytotoxic activities were determined in the MTT assay against HL 60 cells.

Alkaloids↗
PubMed2004

1-Substituted beta-carboline-3-carboxylates with high affinities to the benzodiazepine recognition site.

Naturally occurring derivatives of beta-carboline-3-carboxylic acid bearing acetyl or vinyl groups at C-1 were prepared by Pd-catalyzed cross-coupling reactions of methyl 1-chloro-beta-carboline-3-carboxylate with appropriate organostannanes. Esters with chloro or acetyl groups at C-1 showed high affinity for the brain benzodiazepine recognition site. Thus, in contrast to 1-alkyl and 1-aryl analogs, these beta-carboline-3-carboxylates with electron-withdrawing substituents at C-1 show high affinities.

Animals↗
PubMed2004

A new approach towards ikimine A analogues.

An analogon of the alkylpyridine alkaloid ikimine A (1) was prepared in six steps starting from undec-10-ynoic acid. A key step in this synthesis was a Sonogashira coupling of the alkyne and 3-iodopyridine, followed by hydrogenation of the alkyne, reduction of the ester to the primary alcohol and oxidation to the corresponding aldehyde. This aldehyde was converted to the ikimine A analogon with O-methyl hydroxylamine hydrochloride. This product and the intermediate alkylpyridines were tested in the agar diffusion assay for antibacterial and antifungal activities.

Alkaloids↗
PubMed2003

Norditerpenoid alkaloids from Delphinium species.

From the aerial parts of four Delphinium species 11 known and 3 new norditerpenoid alkaloids have been isolated: from D. dissectum Huth: delavaine A/B, deoxylycoctonine, methyllycaconitine; new: 10-hydroxymethyllycaconitine; from D. excelsum Reichenb.: delcaroline, delectinine, delterine, methyllycaconitine; new: 10-hydroxymethyllycaconitine, 18-O-methyldelterine and 10-hydroxynudicaulidine; from D. grandiflorum L.: delcosine, deltatsine, grandiflorine, methyllycaconitine; from D. triste Fisch.: delcosine, macrocentridine, 14-dehydrodelcosine. The structures of the new alkaloids were established on the basis of MS, 1H, 13C, DEPT, homonuclear COSY, HMQC and HMBC NMR spectroscopic techniques.

Alkaloids↗
PubMed2003

Azasteroids as antifungals.

Azasteroids and derivatives thereof with antifungal potential are reviewed. Special emphasis is put on steroids with nitrogen as part of the steroidal framework, natural substances, and lines of development emerging from them.

Antifungal Agents↗
PubMed2003

Alkaloids from Croton flavens L. and their affinities to GABA-receptors.

Phytochemical investigation of several plants of Croton flavens L. from Barbados has led to the isolation of the tetrahydroprotoberberine alkaloids scoulerine and coreximine, as well as the morphinanedienones salutaridine and its racemic form salutarine, sebiferine, norsinoacutine and flavinantine. In a screening for 3H-GABA displacing activity coreximine showed the highest affinity to the GABA(A) receptor.

Alkaloids↗
PubMed2003

Total synthesis of both enantiomers of the macrocyclic lactone citreofuran.

Both enantiomers of the polyketide-derived lactone citreofuran (4) have been prepared. The enantiopure building blocks were obtained on a chemoenzymatic route ((S)-6) and by a chiral pool synthesis ((R)-6). The crucial step in the synthesis, a macrolactonization, was accomplished under Mitsunobu conditions.

Furans↗