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Norbert Sewald

Publications and source records attributed to Norbert Sewald.

27 records · Page 2Linked to original sources
PubMed2003

First synthesis of a beta(2)-homoamino acid by enantioselective catalysis.

The enantioselective conjugate addition of diethylzinc to the activated nitroolefin methyl 3-nitropropenoate is efficiently catalyzed by copper(I) complexes with BINOL-based enantiopure phosphoramidite ligands. The nitroolefin moiety acts as the predominant Michael acceptor, giving rise to the unambiguous formation of 2-alkyl-3-nitro-propanoates. Moderate to excellent enantioselectivities and high chemical yields are obtained. The product can easily be transformed into a beta(2)-homoamino acid. [reaction--see text]

Amino Acids↗
PubMed2003

Identification of binding mechanisms in single molecule-DNA complexes.

Changes in the elastic properties of single deoxyribonucleic acid (DNA) molecules in the presence of different DNA-binding agents are identified using atomic force microscope single molecule force spectroscopy. We investigated the binding of poly(dG-dC) dsDNA with the minor groove binder distamycin A, two supposed major groove binders, an alpha-helical and a 3(10)-helical peptide, the intercalants daunomycin, ethidium bromide and YO, and the bis-intercalant YOYO. Characteristic mechanical fingerprints in the overstretching behavior of the studied single DNA-ligand complexes were observed allowing the distinction between different binding modes. Docking of ligands to the minor or major groove of DNA has the effect that the intramolecular B-S transition remains visible as a distinct plateau in the force-extension trace. By contrast, intercalation of small molecules into the double helix is characterized by the vanishing of the B-S plateau. These findings lead to the conclusion that atomic force microscope force spectroscopy can be regarded as a single molecule biosensor and is a potent tool for the characterization of binding motives of small ligands to DNA.

Amino Acid Motifs↗
PubMed2002

Conjugate addition of mixed diorganozinc compounds and functionalized organozinc cuprates to nitroolefins.

[reaction: see text] The copper-catalyzed conjugate addition of symmetrical and mixed diorganozinc compounds as well as functionalized diorganozinc cuprates to nitroolefins leads to synthetically versatile nitro compounds in moderate to good yields. Mixed TMSM-organozinc compounds are suitable reagents for conjugate addition, since the TMSM group is not being transferred. Ipso substitution is observed in the absence of a catalytic amount of copper(I) salt. The nitroalkene moiety in 3-nitroacrylates proved to be the predominant Michael acceptor.

Journal Article↗
PubMed1998

Tandem Protocol for the Stereoselective Synthesis of Different Polyfunctional beta-Amino Acids and 3-Amino-Substituted Carbohydrates.

Conjugate addition of homochiral amidocuprates or lithium amides based on (R)-N-(1-phenylethyl)(trimethylsilyl)amine to alpha,beta-unsaturated esters proceeds stereoselectively and allows the synthesis of beta-amino acids. Trapping of the intermediate ester enolate with D(2)O affords the corresponding deuterated compounds. anti-alpha-Alkyl-beta-amino acids are obtained stereoselectively after transmetalation of the lithium/copper ester enolate to the titanium ester enolate and trapping with carbon electrophiles. Both diastereomers of beta-homothreonine, other precursors of 3-amino-substituted carbohydrates, and stereoselectively in position 2 deuterated analogues are formed from enantiomerically pure gamma-alkoxy-substituted enoates. The product distribution observed is complementary to published results regarding 1,4-addition to gamma-silyloxy-substituted enoates. The anti/syn selectivity can be explained by assuming transition state geometries where the delivery of the nitrogen nucleophile is controlled by lithium "chelation" between reagent and substrate. In one case the product configuration can be controlled by the reagent irrespective of the substrate stereochemistry; in other cases the topicity of the addition is complementary to published results. For instance, erythro- or threo-configured 2,3-dideoxy-3-aminopentoses are accessible via this route.

Journal Article↗
PubMed1996

A New Strategy for the Synthesis of alpha-Difluoromethyl-Substituted alpha-Hydroxy and alpha-Amino Acids.

A new method for the preparation of alpha-chlorodifluoromethyl-, alpha-bromodifluoromethyl-, and alpha-difluoromethyl-substituted alpha-hydroxy and alpha-amino acid esters 11, 19-21 is described. The key step of the synthesis is the regioselective alkylation of ketones 5, 7-9 and imines 16-18 with C-nucleophiles. The ketones 7-9 are readily available from 3,3,3-trifluorolactate 1 by a five-step procedure. Subsequent removal of the protecting groups from 19-21 provides the corresponding free amino acids 25, 26, 28.

Journal Article↗
PubMedDate not supplied

Synthesis of marimastat and a marimastat conjugate for affinity chromatography and surface plasmon resonance studies.

Immobilized small-molecule inhibitors are suited for enrichment of biomolecules by affinity chromatography, as it is shown for metalloproteinases and an immobilizable derivative of the hydroxamate-type inhibitor marimastat. A new asymmetric synthesis of marimastat is presented that allows for site-specific attachment to a solid surface, e.g., a chromatography matrix or a surface plasmon resonance sensor chip. The latter technique is shown to be a valuable tool for the optimization of binding and elution conditons of biomolecules in affinity chromatography.

Biosensing Techniques↗