Biomedical subjects

H H Otto

Publications and source records attributed to H H Otto.

At least 19 recordsLinked to original sources

PubMed2005

Capillary electrophoretic separation of enantiomers of amino acids and amino acid derivatives using crown ether and cyclodextrin.

The capillary zone electrophoresis using (+)-18-crown-6-tetracarbonic acid as a chiral selector was a suitable method for the enantiomeric separation of racemates of amino acids and of some amino acid derivatives (esters, dipeptides). The influence of the chemical structure of the compounds on the separation was investigated. After optimization of the separation conditions, baseline separations were obtained for most racemates. The addition of acetonitrile and TBAB yielded an improvement of the separation. Improved selectivity was further observed by the application of a cyclodextrin, HP-beta-CD, in combination with the crown ether.

Amino Acids↗

PubMed2005

Pseudosaccharin amine derivatives: synthesis and elastase inhibitory activity.

Pseudosaccharin amines were synthesized from saccharin either by the reaction of pseudosaccharin chloride with amines, or via thiosaccharin which was treated with amines yielding thiosaccharinates, and their reaction with glacial acetic acid. This route gave lower yields than the first way. The synthesis of alkyl [(1,1-dioxo-benzo[d]isothiazol-3-yl)amino]alkanoates as possible Human Leukocyte Elastase (HLE) inhibitors was realized by the reaction between amino acid esters and pseudosaccharin chloride. Hydrolysis of the esters was possible under aqueous basic conditions. Selected compounds were screened for elastase inhibitory activity. Compounds 4k and 4m were found to be reversible inhibitors of HLE with Ki values of 45 microM and 60 microM.

Amines↗

PubMed2005

Synthesis and properties of chiral N,N-maleoyl derivatives and Diels-Alder reactions with cyclopentadiene.

Maleyl amino acid derivatives were prepared from maleic anhydride and cyclized by reaction with ZnCl2 and hexamethyldisilazane yielding maleoyl derivatives. These derivatives were used as dienophiles in cycloadditions with cyclopentadiene. The isolated norbornene derivatives resulted from an endo addition, and might be interpreted as analogues of thalidomide. For comparing the properties of compounds prepared by this route, some reference compounds were synthesized from endo-bicyclo[2.2.1]hept-2-ene-5,6-dicarboxylic anhydride and amino acid derivatives. All compounds were characterized by spectroscopic methods, their stereochemistry is discussed, and results were compared with results from calculations.

Amino Acids↗

PubMed2003

[Spectroscopic and chromatographic studies on photochemical isomerism of alpha, beta-diunsaturated ketones].

Spectroscopic (UV, IR, NMR, MS) and chromatographic (HPLC, GC) investigations show for alpha,beta-diunsaturated ketones with one double bond fixed in a cyclohexene-, furan- or thiophene ring in most examples a photochemical Z/E-isomerization in solution by the influence of light. Investigations of conformers by IR and NMR however are not influenced during usual operations and light protection is not nessessary.

Chromatography, Gas↗

PubMed2002

Synthesis and properties of N-substituted saccharin derivatives.

Four different routes for the synthesis of saccharin containing peptides were studied. While reactions between saccharin sodium and alpha-halogeno acids were limited to two examples, reactions of sulfobenzoic anhydride (4) or saccharin-N-carboxylate (6) with amino acid esters yielded the ring opened products 5 and 7. Finally, we found, that the reaction between the benzoxathiol derivative 8 and amino acid derivatives represents a versatile route to the peptidic compounds 9 and 11. Hydrolysis and hydrogenolysis were studied, and by combination of the different routes the "saccharin tripeptides" 18 were obtained. Structures and stereochemistry were elucidated by spectroscopic and chromatographic methods. Selected compounds were tested as sweeteners or as inhibitors of elastase, but no exiting results were found.

Chromatography, High Pressure Liquid↗

PubMed2001

beta-lactam derivatives as enzyme inhibitors: carboxy peptidyl derivatives of (S)-4-oxoazetidine-2-carboxylate as peptidomimetics.

4-Oxoazetidine-2-carboxylic acid, protected at the nitrogen by silyl groups, was coupled with amino acid and oligopeptide esters. Desilylation and deprotection of the amino acid residues yielded the free beta-lactam peptides. Structure and properties were elucidated by spectroscopic methods and discussed. Some selected compounds were tested as fibrinogen inhibitors and for thrombocyte aggregation. None of the compounds showed any activity up to a concentration of 10(-5) Mol/l. Some other compounds exhibited a weak inhibitory activity against elastase (PPE).

Enzyme Inhibitors↗

PubMed2001

Chiral separation of amino acid esters by micellar electrokinetic chromatography.

Micellar electrokinetic chromatography (MEKC) was used for the chiral separation of uncharged analytes (C- and N-protected amino acids). Sodium dodecyl sulfate (SDS) was the micelle forming agent, and different cyclodextrin (CD) derivatives were added as chiral selectors. Suitable conditions for the enantioseparation were found by variation of the separation conditions. The influence of addition of organic solvents like acetonitrile or methanol, and other chiral additives (camphor-10-sulfonic acid, malic acid) was examined. The addition of an organic modifier resulted in different effects on micelle formation, and thereby on the separation. The used chiral additives did not improve the selectivity. Furthermore, dependence of the electroosmotic flow (EOF), and the capacity factors on the concentration of CDs was investigated. Increasing the CD concentration, both the EOF to a smaller extent as well as the capacity factors decrease. Nevertheless, the enantioseparation is improved with a CD-concentration up to 30 mM. Higher CD-concentrations reduce the separation of the analytes.

Acetonitriles↗

PubMed2001

beta-Lactam derivatives as enzyme inhibitors: derivatives of (E)-2-[(RS)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetidin-3-ylidene]propionic acid.

The 1,4-diaryl disubstituted azetidin-2-one (beta-lactam) 1 is transformed into the 3-methylidene derivative (E)-2-[(RS)-1-(4-methoxyphenyl)-2-oxo-4-phenylazetidin-3-ylidene]propionic acid (3), and then, using the DCC/NHS method reacted with amino acid esters and dipeptide esters forming 3-(peptidyl)-beta-lactams 5 and 7. Structures and properties are evaluated mainly by spectroscopic methods and discussed. As molecular modeling experiments might suggest a potential activity as inhibitors of PPE(HLE), a number of selected compounds has been tested in an enzyme assay. But none of them showed any remarkable inhibitory activity. Evaluation of the data was done with the new program EnKinPlot.

Amino Acids↗

PubMed2000

beta-Lactam derivatives as enzyme inhibitors: 1-peptidyl derivatives of 4-phenylazetidin-2-one as inhibitors of elastase and papain.

N-Peptidyl substituted azetidin-2-ones were synthesized and evaluated as inhibitors of the serine protease elastase, and the cysteine protease papain. All compounds were synthesized from 4-phenylazetidin-2-one, either from the racemate or from the pure enantiomers. The (S)-enantiomer was prepared by enantioselective synthesis from (S)-beta-phenyl-beta-alanine, while the (R)-enantiomer was obtained by enzymatic resolution with alpha-chymotrypsin. N-Alkylation with bromoacetates introduced a spacer group which, after hydrolysis to the free acid, was acylated with amino acid esters or di- or tripeptide esters. The enzymatic assays proved some derivatives to be effective inhibitors of PPE and/or papain. N-BOC protected amino acid derivatives without a spacer group inhibited PPE reversibly, while derivatives with spacer group showed either weak or no inhibitory properties. On the other hand, papain was inactivated irreversibly by ethyl (RS)-2-oxo-4-phenylazetidin-1-acetate. The highest inhibitory activity against papain was found for the diastereomers of N-(2-oxo-4-phenylazetidin-1-acetyl)-L-alanyl-L-valine benzyl ester, a compound with a spacer group.

Amino Acids↗

PubMed2000

beta-Lactam derivatives as enzyme inhibitors: N-substituted derivatives of (S)-4-oxoazetidine-2-carboxylate as inhibitors of elastase and papain.

N-Alkyl and N-acyl substituted 4-oxoazetidine-2-carboxylates are synthesized and evaluated as inhibitors of the proteases porcine pancreatic elastase (PPE) and papain. The compounds are obtained by alkylation or acylation at the nitrogen of benzyl (S)-4-oxoazetidine-2-carboxylate, which is synthesized by a modified literature procedure. The enzymatic assays prove some derivatives to be effective inhibitors of PPE and/or papain. The N-BOC protected amino acid derivatives 10 and 13 inhibit PPE reversibly with KI-values in the micromolar range. On the other hand, papain is inactivated irreversibly by benzyl (S)-2-(benzyloxycarbonyl)azetidin-1-acetate (6).

Animals↗

PubMed1996

Sulfogriseofulvin derivatives. synthesis by [4 + 2]cycloaddition, structure, properties, crystal structure analysis, and antifungal activity of spiro[1,3-benzoxathiole-2,1'-cyclohex-2'-en]-4'-one 3,3-dioxides.

Syntheses of substituted, especially of fluoro substituted benzoxathiole 1,1-dioxides, are described. These derivatives were transformed via the Peterson olefination into substituted 2-alkylidene derivatives 27. Diels-Alder reactions of 27 with 1,1-dimethoxy- and 1-methoxy-3-trimethylsiloxy-1,3-butadiene (30, 32) gave sulfone analogues 31 of griseofulvin (named sulfogriseofulvins). From Z-27, a number of cis-isomers with the relative stereochemistry of griseofulvin (cis-31) was prepared, and from E-isomers of 27, compounds (trans-31) with relative stereochemistry of epigriseofulvin were obtained. Some related compounds (33, 38) are synthesized by slight modifications. The stereochemistry is established by spectroscopic methods and crystal structure analyses. The compounds 31 were tested against three species of dermatophytes. The biological activities were all significantly lower than that of griseofulvin.

Antifungal Agents↗

PubMed1996

3-Methylidene-beta-lactams as potential inhibitors of beta-lactamases. Part 1: Synthesis of alpha-substituted derivatives from imines by Reformatzky reaction with chlorotrimethylsilane, silylation and Peterson olefination.

A new variation of the Reformatzy reaction with use of I2/zinc and chlorotrimethylsilane in THF and a shortened work-up is described allowing the synthesis of a wide variety of substituted beta-lactams 3 in fairly good yield. These lactams are silylated according to the Peterson reaction yielding by reactions with appropriate carbonyl compounds E/Z-mixturs of the substituted 3-methylidene beta-lactams 7, 8 and 10. The isomers are separated by CC and completely characterized by spectroscopic methods, mainly 1H NMR spectroscopy. Condensation of the 3-formyl methylidene derivative 10 with amines or malonate yields the conjugated products 11, and from the isopropylidene derivative 6 the pyridinium sulfonate 14 is prepared via 12 and 13. All methylidene beta-lactams are prepared as model compounds for studying their activity against beta-lactamases and for elucidating the mechanism of action.

Alkenes↗

PubMed1984