Biomedical subjects

August Wilhelm Frahm

Publications and source records attributed to August Wilhelm Frahm.

4 recordsLinked to original sources

PubMed2006

Bicyclic glutamic acid derivatives.

For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

Amino Acids, Cyclic↗

PubMed2005

Rigid nonproteinogenic cyclic amino acids as ligands for glutamate receptors: trans-tris(homoglutamic) acids.

The second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids reported herein proceeds via Strecker reaction of chiral ketimines, obtained from condensation of racemic 2-ethoxycarbonylmethylcyclopentanone and commercially available (S)- and (R)-1-phenylethylamine, respectively. In the key stereodifferentiating step, the cyanide addition leads to mixtures of diastereomeric alpha-amino nitrile-esters, the composition of which is independent of the reaction temperature and the type of the solvent, respectively. Hydrolysis of the alpha-amino nitrile-esters with concentrated H(2)SO(4) yielded diastereomeric mixtures of secondary alpha-amino amido-esters, which after separation were hydrogenolyzed and hydrolyzed each to the enantiomeric trans-1-amino-2-carboxymethylcyclopentanecarboxylic acids. Their configuration was completely established by NMR methods, CD spectra, and X-ray analysis of the trans-1S,2R-configured secondary alpha-amino amido-ester. In receptor binding assays and functional tests, trans-1S,2R-1-amino-2-carboxymethylcyclopentanecarboxylic acid hydrochloride was found to behave as a selective mGluR(2)-antagonist without relevant binding properties at iGluRs.

Amino Acids, Cyclic↗

PubMed2004

Conformational analysis of the biflavanoid GB2 and a polyhydroxylated flavanone-chromone of Cratoxylum neriifolium.

Three compounds, namely the interesting biflavanonol GB-2(naringenin 1-3, 11-8-dihydroquercetin, 1), 1-4',1-5,11-5,1-7,11-7-pentahydroxyflavanone(l-3,11-8)chromone [naringenin-(3 -8) 5,7-dihydroxychromone, 21 and stigmasterol, have been isolated from the leaves of Cratoxylum neriifolium Kurz. Compounds 1 and 2 show rotameric behavior due to the presence of a single bond between the highly substituted flavanone and flavanonol part and the flavanone and chromone part, respectively. Complete NMR spectral assignments of 1 and 2 have been done at 27 C and 90 C for the first time followed by a study of conformational behavior at room temperature by ROESY.

Clusiaceae↗

PubMed2002

Separation and first structure elucidation of Cremophor EL-components by hyphenated capillary electrophoresis and delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry.

The polyethoxylated heterogeneous components of the so far poorly characterized nonionic emulsifier Cremophor EL (polyoxyl 35 castor oil) (CrEL) were fractionated by cyclodextrin-modified micellar electrokinetic capillary chromatography (CD-MEKC). Due to the low UV absorbance of most of the CrEL-components an indirect UV detection was used with phenobarbital-sodium as background absorber. For a precise assignment of the resulting peaks to the corresponding components capillary electrophoresis (CE) had to be combined with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS) as detection system. For this purpose, the fractionating robot Probot was employed which enables both the on-line fractionation of the CE eluate on a MALDI target during the electrophoretic separation and the simultaneous dosage of the MALDI matrix solution. The applied CrEL amount was optimized by varying the CE injection parameters time, pressure and concentration of the sample in order to obtain homologue peak series of sufficient intensity without decreasing the separation efficiency. Evaluation of the mass spectra was performed by comparing the residue masses of the homologue peak series with the calculated residue masses of potential CrEL-components. However, the high number of polyethoxylated components leads to overlapping of homologue peak series with isobaric residue masses. These isobaric interferences were detected by a high mass accuracy of the measurements (obtained by internal calibration with polyethylene glycol (PEG) 1000 and by means of the residue mass plot, the newly developed evaluation method. The combination of these techniques allowed the first detailed structure analysis of the CrEL-components showing glycerol polyoxyethylene (POE) monoricinoleate and POE monoricinoleate to be the two main components of the emulsifier. Furthermore, the coupling of CE with DE-MALDI-TOF-MS is generally applicable to the fractionation and identification of polymers.

Calibration↗